Systems and methods for shuttle mode radiation delivery

ABSTRACT

Systems and methods for shuttle mode radiation delivery are described herein. One method for radiation delivery comprises moving the patient platform through the patient treatment region multiple times during a treatment session. This may be referred to as patient platform or couch shuttling (i.e., couch shuttle mode). Another method for radiation delivery comprises moving the therapeutic radiation source jaw across a range of positions during a treatment session. The jaw may move across the same range of positions multiple times during a treatment session. This may be referred to as jaw shuttling (i.e., jaw shuttle mode). Some methods combine couch shuttle mode and jaw shuttle mode. Methods of dynamic or pipelined normalization are also described.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.17/150,977, filed Jan. 15, 2021, which is a continuation of U.S. patentapplication Ser. No. 16/814,867, filed Mar. 10, 2020, now issued as U.S.Pat. No. 10,912,950, which is a continuation of U.S. patent applicationSer. No. 16/138,631, filed Sep. 21, 2018, now issued as U.S. Pat. No.10,617,888, which claims priority to U.S. Provisional Patent ApplicationNo. 62/562,212, filed Sep. 22, 2017, each of which is herebyincorporated by reference in its entirety.

BACKGROUND

Tumor motion modulates dose delivery in radiation therapy, oftenresulting in uneven dose distribution across a target region. Dosemodulation may be caused by an interplay between the moving parts in aradiation therapy system (e.g., the multi-leaf collimator (MLC), themovable gantry upon which the therapeutic radiation source and the MLCare mounted, the patient platform, etc.) and the motion of the tumor.For example, because lung tumors are subject to a large range of motionthat result in the tumors moving into and out of the treatment planeunpredictably, it can be challenging to deliver the prescribed radiationdose to the tumor.

Several solutions have been proposed to mitigate unwanted dosemodulation. One solution for a tomotherapy machine with a rotatablegantry is called dose painting and involves arcing the therapeuticradiation source over the patient treatment region twice at a particularcouch location. That is, first moving therapeutic radiation source inthe clockwise and then in the anti-clockwise direction. Dose paintingmethods may reduce the variability in the dose delivered, but at thecost of increased treatment time. Other solutions for motion managementand dose artifact reduction include coached breathing, breath hold, andrespiratory gating. Instructing the patient to hold their breath duringa radiation beam pulse may help limit the range of motion for the tumor,but depending on the health of the patient, it may not be possible toensure consistent breath hold. Improved systems and methods for ensuringthe uniform delivery of radiation dose to a moving target region aredesirable.

SUMMARY

Disclosed herein are systems and methods for shuttle mode radiationdelivery. Shuttle mode radiation delivery may be used in helicaltomotherapy, with or without continuous platform motion or steppedplatform motion. A radiation therapy system for helical tomotherapy maycomprise a rotatable gantry that rotates about a patient treatmentregion, a therapeutic radiation source mounted on the rotatable gantry,and a patient platform or couch movable within the patient treatmentregion. In some variations, the system may further comprise beam-shapingelements disposed in the beam path of the therapeutic radiation source,including a jaw that is movable (e.g., along the direction of movementof the patient platform) and a dynamic multi-leaf collimator (MLC) thatshapes the radiation emitted by the therapeutic radiation source. Somevariations of a radiation therapy system may further comprise one ormore PET detectors. A radiation delivery system may be configured tomove the patient platform through the same segments of the patienttreatment region multiple times during a treatment session. This may bereferred to as patient platform or couch shuttling (i.e., couch shuttlemode). A system for radiation dose delivery may be configured to movethe jaw across a range of positions while the patient platform movesthrough (continuously or in steps) the patient treatment region during atreatment session. The jaw may move across the same range of positionsmultiple times during a treatment session. This may be referred to asjaw shuttling (i.e., jaw shuttle mode), which may help provide uniformjaw dwell time over a patient target region. Some radiation deliverysystems may be configured to perform both couch shuttling and jawshuttling. The systems and methods described herein may help to mitigatedose modulation due to tumor movement and promote homogenous dosedelivery to target regions. For example, the systems and methodsdescribed herein may help to mitigate dose modulation due to tumormovement and jaw/MLC interplay artifacts, and may also compensate fordose modulation due to low-frequency motion of tumors (e.g., tumormotion having a period on the order of tens of seconds, tumor shiftsover multiple seconds).

One variation of a radiation delivery system may comprise a gantry, atherapeutic radiation source mounted on the gantry and configured toapply radiation in a radiation treatment beam plane, a platform movablerelative to the gantry, and a controller in communication with thegantry, the radiation source, and the platform. The controller may beconfigured to move a patient located on the platform from a firstlocation to a second location such that the patient passes through theradiation treatment beam plane while acquiring a first set of imagingdata, and apply a first quantity of radiation with the radiation sourceas the patient passes through the radiation treatment beam plane, wherethe first quantity of radiation is derived from the first set of imagingdata. The controller may be further configured to move the patient fromthe second location to the first location such that the patient passesthrough the radiation treatment beam plane while acquiring a second setof imaging data, and apply a second quantity of radiation with theradiation source as the patient passes through the radiation treatmentbeam plane, where the second quantity of radiation is derived from thesecond set of imaging data and the second quantity of radiation isdifferent from the first quantity of radiation.

The first quantity of radiation may be determined based on the first setof imaging data, and the second quantity of radiation may be determinedbased on the second set of imaging data. The first and/or second sets ofimaging data may include, for example, positron annihilation emissiondata, kV X-ray data, or MRI sub-samplings in k space. The controller maybe further configured to calculate a normalization factor k₂ based onthe first quantity of radiation, and the second quantity of radiationmay be determined at least in part using the normalization factor andthe second set of imaging data. The controller may be further configuredto acquire a pre-scan image (X_(prescan)) of a target region of thepatient located on a radiation therapy system platform, and to calculatea first normalization factor k₁ based on the pre-scan image(X_(prescan)), where the normalization factor k₂ is a secondnormalization factor. Moving the patient from the first location to asecond location may define a first shuttle pass, and moving the patientfrom the second location to the first location may define a secondshuttle pass, where the controller may be configured to select a numberof shuttle passes (N) and a cumulative dampening factor (a), andcalculate a normalized dampening factor (β), where

$\beta_{i} = \frac{\alpha^{i - 1}}{\sum_{j = 1}^{N}\alpha^{j - 1}}$for i=1, . . . , N. Furthermore, the first quantity of radiation(D_(1,calculated)) may be calculated based on the first set of imagingdata and scaled by the first normalization factor k₁. The first quantityof radiation (D_(1,calculated)) may be calculated by multiplying thefirst set of imaging data with a radiation-firing matrix (RFM) of atreatment plan, spatially-filtered with a bitmask BFZ that correspondsto a spatial location of the target region, and multiplied by the firstnormalization factor k₁. Calculating the second normalization factor k₂may comprise calculating a predicted cumulative dose by summing the dosedelivered D_(1,calculated) over (N−1) passes of radiation delivery(D_(1,predicted cumulative)) and calculating the difference between aplanned dose (Doan) and the first quantity of radiation(D_(1,calculated)), and taking the ratio of the dose difference over thepredicted cumulative dose (D_(1,predicted cumulative)). The secondquantity of radiation (D_(2,calculated)) may be calculated bymultiplying the second set of imaging data with the RFM of the treatmentplan, spatially-filtered with a bitmask BFZ that corresponds to aspatial location of the target region, and multiplied by the firstnormalization factor k₂. In some variations, the first normalizationfactor k₁ may be determined by

$k_{1} = \frac{D_{plan}}{D_{0,{raw}}}$where D_(plan) is a radiation dose or fluence as specified in thetreatment plan, and D_(0,raw) is a radiation fluence given by

$\left( {D_{prescan} \times \frac{{treatment}{time}}{{prescan}{imaging}{time}}} \right),{{{where}D_{prescan}} = {A \cdot {\left( {X_{prescan}*{RFM}} \right) \circ {BFZ}}}},$D_(prescan) is the radiation fluence calculated by multiplying thepre-scan image (X_(prescan)) with a radiation-firing matrix (RFM) of atreatment plan, spatially-filtered with a bitmask BFZ that correspondsto a spatial location of the target region, and multiplied by a dosecalculation matrix. Calculating the predicted cumulative dose(D_(1,predicted cumulative)) may comprise adding any negative radiationfluences resulting from multiplying the first set of imaging data with aradiation-firing matrix (RFM) of a treatment plan, spatially-filteredwith a bitmask BFZ that corresponds to a spatial location of the targetregion.

Another variation of a radiation delivery system for deliveringradiation during a treatment session may comprise a gantry, atherapeutic radiation source mounted on the gantry, an imaging systemmounted on the gantry, and a controller in communication with thegantry, the radiation source, and the imaging system. The controller maybe configured to acquire imaging data of a patient located on a platformwith the imaging system, and apply a quantity of radiation to thepatient with the radiation source to deliver a treatment planned amountof radiation D_(plan), where the quantity of radiation is derived fromthe acquired imaging data. The controller may be further configured tostop the application of radiation o the patient, store the amount ofradiation applied to the patient prior to stopping the application ofradiation D_(delivered,pre-interrupt) and the location of the platformwhen the radiation application was stopped, and resume radiationapplication to the patient while acquiring additional imaging data,where a second quantity of radiation applied to the patient is derivedfrom the additional imaging data and adjusted according to a differencebetween D_(plan) and D_(delivered,pre-interrupt).

Resuming radiation application may comprise moving the patient platformback to the location of the platform when the application of radiationwas stopped. The quantity of applied before stopping the application ofradiation may be a first quantity of radiation and may be derived fromimaging data x_(i) acquired during the treatment session before stoppingthe application of radiation. Furthermore, the first quantity ofradiation may be derived by multiplying acquired imaging data x_(i) witha radiation-firing matrix RFM and applying a biological firing zonebitmask BFZ, where the RFM and the BFZ are calculated during a treatmentplanning session. In some variations, applying a quantity of radiationto the patient may comprise applying a first pass of radiation whenmoving the patient platform from a first location to a second locationthrough a therapeutic radiation beam plane while acquiring a first setof imaging data x₁, where the quantity of radiation emitted during thefirst pass (D_(1,calc)) may be derived by multiplying the first set ofimaging data x₁ with the radiation-firing matrix RFM and applying thebiological firing zone bitmask BFZ to obtain D_(1,raw) and scalingD_(1,raw) by a first normalization factor k₁. Furthermore, in somevariations the first normalization factor k₁ may be calculated bycalculating a radiation quantity D_(0,raw) by multiplying a pre-scanimage of the patient acquired during the treatment session with theradiation-firing matrix RFM and applying the biological firing zonebitmask BFZ, calculating a cumulative predicted doseD_(0,predicted cumulative) by multiplying D_(0,raw) by a total numberradiation passes N in the treatment session; and taking a ratio betweenD_(plan) and the cumulative predicted dose D_(0,predicted cumulative).In some variations, applying a quantity of radiation to the patient mayfurther comprise applying a second pass of radiation when moving thepatient platform from the second location to the first location throughthe therapeutic radiation beam plane while acquiring a second set ofimaging data x₂, where the quantity of radiation emitted during thesecond pass (D_(2,calc)) is derived by multiplying the second set ofimaging data x₂ with the radiation-firing matrix RFM and applying thebiological firing zone bitmask BFZ to obtain D_(2,raw), and scalingD_(2,raw) by a second normalization factor k₂. Stopping the applicationof radiation to the patient may comprise stopping the application ofradiation during the second pass of radiation. Additionally oralternatively, resuming radiation application to the patient maycomprise acquiring a resumed set of imaging data x_(2,resumed), andemitting a quantity of radiation, where the quantity of radiation may bederived by multiplying the resumed set of imaging data x_(2,resumed)with the radiation-firing matrix RFM and applying the biological firingzone bitmask BFZ to obtain D_(2,raw,post-interrupt), and scalingD_(2,raw,post-interrupt) by the second normalization factor k₂, wherethe quantity of radiation may be applied before stopping the applicationof radiation is D_(2,raw,pre-interrupt). Furthermore, resuming radiationapplication to the patient may further comprise applying a third pass ofradiation when moving the patient platform from the first location tothe second location through the therapeutic radiation beam plane whileacquiring a third set of imaging data x₃, where the quantity ofradiation emitted during the third pass may be derived by multiplyingthe third set of imaging data x₃ with the radiation-firing matrix RFM,applying the biological firing zone bitmask BFZ and scaling by a thirdnormalization factor k₃. In some variations, the third normalizationfactor k₃ may be calculated by calculating a difference between D_(plan)and a cumulative quantity of radiation applied in the first passD_(1,calc) and the second pass D_(2,calc), calculating a cumulativepredicted dose D_(2,predicted cumulative) by multiplying(D_(2,raw,pre-interrupt)+D_(2,raw,post-interrupt)) by N−3, and taking aratio between (D_(plan)−(D_(1,calc)+D_(2,calc))) and the cumulativepredicted dose D_(2,predicted cumulative). In some variations, stoppingthe application of radiation to the patient may comprise stopping theapplication of radiation during the second pass of radiation andresuming radiation application to the patient may comprise acquiring asecond pre-scan image of the patient, moving the patient platform backto the location of the patient platform when the application radiationwas stopped, and acquiring a resumed set of imaging data x_(2,resumed)and emitting a quantity of radiation derived by multiplying the resumedset of imaging data x_(2,resumed) with the radiation-firing matrix RFMand applying the biological firing zone bitmask BFZ to obtainD_(2,raw,post-interrupt), and scaling D_(2,raw,post-interrupt) by aresumed normalization factor k_(2_resumed), where the quantity ofradiation applied before stopping the application of radiation isD_(2,raw,pre-interrupt). Furthermore, the resumed normalization factork_(2_resumed) may be calculated by calculating a radiation quantityD_(2,raw,post-interrupt) by multiplying the second pre-scan image of thepatient with the radiation-firing matrix RFM and applying the biologicalfiring zone bitmask BFZ, calculating a cumulative predicted doseD_(2,predicted cumulative) by multiplying(D_(2,raw,pre-interrupt)+D_(2,raw,post-interrupt)) by N−2, and taking aratio between D_(plan) and the cumulative predicted doseD_(2,predicted cumulative). Resuming radiation application to thepatient may further comprise applying a third pass of radiation whenmoving the patient platform from the first location to the secondlocation through the therapeutic radiation beam plane while acquiring athird set of imaging data x₃, where the quantity of radiation emittedduring the third pass is derived by multiplying the third set of imagingdata x₃ with the radiation-firing matrix RFM, applying the biologicalfiring zone bitmask BFZ and scaling by a third normalization factor k₃.The third normalization factor k₃ may be calculated by calculating adifference between D_(plan) and a cumulative quantity of radiationapplied in the first pass D_(1,calc) and the second pass D_(2,calc),calculating a cumulative predicted dose D_(2,predicted cumulative) bymultiplying (D_(2,raw,pre-interrupt)+D_(2,raw,post-interrupt)) by N−3;and taking a ratio between (D_(plan)−(D_(1,calc)+D_(2,calc))) and thecumulative predicted dose D_(2,predicted cumulative).

Another variation of a radiation delivery system may comprise a gantry,a therapeutic radiation source mounted on the gantry and configured toapply radiation in a radiation treatment beam plane, a plurality of PETdetectors mounted on the gantry, a platform movable relative to thegantry, and a controller in communication with the gantry, thetherapeutic radiation source, and the platform. The controller may beconfigured to acquire an image of a patient on the platform, calculate anormalization factor based on the image of the patient, and deliverradiation to the patient across a pre-selected number of shuttle passes.In each shuttle pass, the controller may be configured to update aradiation-firing matrix of a treatment plan with the calculatednormalization factor, move the platform from a first pre-determinedlocation to a second pre-determined location and back to the firstpre-determined location such that a target region in the patient crossesthe radiation treatment beam plane at least twice, acquire PET datausing the PET detectors, deliver radiation to the patient based on theupdated radiation-firing matrix and acquired PET data, calculate fluencedelivered to the patient when the platform has moved back to the firstpre determined location, calculate a fluence difference between thefluence delivered to the patient and a treatment plan fluence andcalculate an updated normalization factor based on the fluencedifference.

The PET detectors may be co-planar with the radiation treatment beamplane, and in some variations the acquired image may be a PET image. Forexample, the calculation of the normalization factor may comprisecalculating a mean of a PET intensity of the target region in theacquired PET image. The pre-selected number of shuttle passes may beeven. For example, the pre selected number of shuttle passes may be twoor more. In some variations, calculating an updated normalization factormay comprise calculating a mean fluence value of the radiation emittedby the therapeutic radiation source. Additionally or alternatively,calculating an updated normalization factor may comprise calculating aratio of a mean planned dose value of radiation to the target region anda mean delivered dose value of the radiation. Delivering radiation basedon the updated radiation-firing matrix and acquired PET data maycomprise multiplying the updated radiation-firing matrix with one ormore lines-of-response (LORs) of the acquired PET data to derive adelivery fluence map and generating radiation using the therapeuticradiation source according to the delivery fluence map. In somevariations, the radiation delivery system may further comprise a movablejaw disposed over the therapeutic radiation source and a multi-leafcollimator coupled to the jaw, where the treatment plane is defined by aposition of the movable jaw and a configuration of the multi-leafcollimator relative to the therapeutic radiation source. In thesevariations, the controller may be configured to move the movable jawfrom a first jaw location to a second jaw location back to the first jawlocation when radiation is delivered to the patient. In some variations,the controller may be configured to calculate a predicted dose and dosevalue histogram by adjusting the image by the calculated normalizationfactor.

Another variation of a radiation delivery system may comprise a gantry,a therapeutic radiation source, a radiation therapy system platform, anda controller. A movable jaw and a multi-leaf collimator may both bedisposed in a radiation beam path of the radiation source, and aposition of the movable jaw and a configuration of the multi-leafcollimator relative to the radiation source may define a treatmentplane. Additionally, the controller may be in communication with thegantry, the radiation source, and the radiation therapy system platform.The controller may be configured to (a) move a patient located on theplatform by moving the platform from a first pre-determined location toa second pre-determined location such that one or more target regions inthe patient crosses the treatment plane; and (b) deliver radiation tothe patient with the radiation source when a portion of the one or moretarget regions crosses the treatment plane, wherein delivery of theradiation comprises moving the movable jaw from a first jaw location toa second location back to the first jaw location while emittingradiation from the radiation source before moving to the next platformlocation.

Moving the platform may comprise moving the platform in a series ofpre-defined incremental patient platform locations, and deliveringradiation to the patient may comprise delivering radiation at eachplatform location where the target regions cross the treatment plane.Moving the platform comprises translating the platform along alongitudinal axis and wherein moving the movable jaw comprises movingthe jaw such that the treatment plane shifts along the longitudinalaxis. Moving the movable jaw may shift the treatment plane from about 3cm to about 6 cm along the longitudinal axis and/or at a speed of about0.5 cm/s. Furthermore, the controller may be configured to acquire animage of the patient before radiation is delivered to the patient. Forexample, the system may comprise a plurality of PET detectors configuredto acquire PET data including lines-of-response (LORs), where deliveringradiation to the patient may comprise multiplying a radiation-firingmatrix of a treatment plan with one or more LORs to derive a deliveryfluence map and generating radiation using the therapeutic radiationsource according to the delivery fluence map. The acquired image may bea PET image. In some variations, the controller may be configured torepeat steps (a) and (b) a pre-selected number of shuttle passes. Forexample, the pre-selected number of shuttle passes may be two or more.

Another variation of a radiation delivery system may comprise a gantry,a therapeutic radiation source, and a controller in communication withthe gantry and the radiation source. The controller may be configured tocalculate a radiation fluence delivered to a patient target regionduring a previous radiation delivery session, compare the deliveredradiation fluence to the target region with treatment plan fluence tothe target region and calculate a fluence difference, calculate aradiation-firing matrix based on the calculated fluence difference; anddeliver radiation to the patient in a subsequent radiation deliverysession based on the calculated radiation-firing matrix and PET dataacquired during the subsequent radiation delivery session. Comparing thedelivered radiation fluence and the planned radiation fluence maycomprise comparing a mean radiation fluence delivered to the targetregion with a mean treatment plan fluence to the target region andcalculating a fluence difference by taking the difference between themean delivered radiation fluence and the mean treatment plan fluence. Insome variations, PET data may comprise line-of-response (LOR) data.

One variation of a method for radiation delivery may comprise acquiringan image of a patient on a radiation therapy system platform, where theradiation therapy system further comprises a therapeutic radiationsource configured to apply radiation in a treatment plane and aplurality of PET detectors, calculating a normalization factor based onthe image of the patient, and delivering radiation to the patient acrossa pre-selected number of shuttle passes. Each shuttle pass may compriseupdating a radiation-firing matrix of a treatment plan with thecalculated normalization factor, moving the patient platform from afirst pre-determined location to a second pre-determined location suchthat a target region in the patient crosses the treatment plane once,acquiring PET data using the PET detectors, delivering radiation to thepatient based on the updated radiation-firing matrix and acquired PETdata. When the platform has moved to the second pre-determined location,the radiation therapy system may calculate the fluence delivered to thepatient, calculate a fluence difference between the fluence delivered tothe patient and a treatment plan fluence, and calculate a fluencedifference between the fluence delivered to the patient and a treatmentplan fluence. The PET detectors may be co-planar with the treatmentplane. Acquiring an image may comprise acquiring a PET image. Thepre-selected number of shuttle passes may be even, e.g., two or more.Calculating the normalization factor may comprise calculating a mean ofa PET intensity of the target region in the acquired PET image.Calculating an updated normalization factor may comprise calculating amean fluence value of the radiation emitted by the therapeutic radiationsource. Alternatively or additionally, calculating an updatednormalization factor may comprise calculating a ratio of a mean planneddose value of radiation to the target region and a mean delivered dosevalue of the radiation. Delivering radiation based on the updatedradiation-firing matrix and acquired PET data may comprise multiplyingthe updated radiation-firing matrix with one or more lines-of-response(LORs) of the acquired PET data to derive a delivery fluence map andgenerating radiation using the therapeutic radiation source according tothe delivery fluence map. The radiation therapy system may furthercomprise a movable jaw disposed over the therapeutic radiation sourceand a multi-leaf collimator coupled to the jaw, where the treatmentplane may be defined by a position of the movable jaw and aconfiguration of the multi-leaf collimator relative to the therapeuticradiation source. The method may further comprise moving the movable jawfrom a first jaw location to a second jaw location back to the first jawlocation while delivering radiation to the patient. Some variations mayfurther comprise calculating a predicted dose and dose value histogramby adjusting the image by the calculated normalization factor.

Another variation of a method for radiation delivery may comprise (a)moving a patient on a radiation therapy system platform from a firstpre-determined location to a second pre-determined location where theradiation therapy system may further comprise a therapeutic radiationsource, a movable jaw and a multi-leaf collimator both disposed in aradiation beam path of the therapeutic radiation source, where aposition of the movable jaw and a configuration of the multi-leafcollimator relative to the therapeutic radiation define a treatmentplane, and where moving the patient from the first location to thesecond location causes one or more target regions in the patient tocross the treatment plane, and (b) delivering radiation to the patientwhen a portion of the one or more target regions crosses the treatmentplane. Delivering radiation may comprise moving the movable jaw from afirst jaw location to a second jaw location back to the first jawlocation while emitting radiation from the therapeutic radiation sourcebefore moving to the next platform location. Moving the patient platformmay comprise moving the platform in a series of pre-defined incrementalpatient platform locations, and where delivering radiation to thepatient comprises delivering radiation at each platform location wherethe target regions cross the treatment plane. Moving the platform maycomprise translating it along a longitudinal axis and where moving themovable jaw comprises moving the jaw such that the treatment planeshifts along the longitudinal axis. Moving the movable jaw may shift thetreatment plane from about 3 cm to about 6 cm along the longitudinalaxis. Moving the movable jaw shifts the treatment plane at a speed ofabout 0.5 cm/s. The method may further comprise acquiring an image ofthe patient before delivering radiation to the patient. The radiationtherapy system may further comprise a plurality of PET detectorsconfigured to acquire PET data including lines-of-response (LORs), andwhere delivering radiation to the patient comprises multiplying aradiation-firing matrix of a treatment plan with one or more LORs toderive a delivery fluence map and generating radiation using thetherapeutic radiation source according to the delivery fluence map. Theacquired image may be a PET image. The method may further compriserepeating steps (a) and (b) a pre-selected number of shuttle passes,where the pre-selected number of shuttle passes is two or more.

Another variation of a method for radiation delivery may comprisecalculating a radiation fluence delivered to a patient target regionduring a previous radiation delivery session, comparing the deliveredradiation fluence to the target region with treatment plan fluence tothe target region and calculate a fluence difference, calculating aradiation-firing matrix based on the calculated fluence difference, anddelivering radiation to the patient in a subsequent radiation deliverysession based on the calculated radiation-firing matrix and PET dataacquired during the subsequent radiation delivery session. Comparing thedelivered radiation fluence and the planned radiation fluence maycomprise comparing a mean radiation fluence delivered to the targetregion with a mean treatment plan fluence to the target region andcalculating a fluence difference by taking the difference between themean delivered radiation fluence and the mean treatment plan fluence. Insome variations, PET data may comprise line-of-response (LOR) data.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A depicts one variation of a radiation therapy system.

FIG. 1B depicts a perspective component view of a radiation therapysystem (e.g., the radiation therapy system of FIG. 1A).

FIG. 1C depicts one variation of a beam-shaping module.

FIG. 2A depicts a plot that represents the frequency spectrum ofbreathing motion.

FIG. 2B depicts a plot that represents the motion of a target regionduring a treatment session.

FIG. 2C depicts planned dose distribution plots.

FIG. 2D depicts a delivered dose distribution plot.

FIG. 3A depicts a plot that represents the motion of a target regionduring a treatment session.

FIG. 3B depicts a plot that represents the motion of a target regionduring a treatment session in shuttle mode.

FIG. 3C depicts a table representing delivered dose to a target regionafter one shuttle pass and after eight shuttle passes.

FIG. 3D depicts planned dose distribution plots.

FIG. 3E depicts a delivered dose distribution plot for radiationdelivered in shuttle mode.

FIG. 4 depicts a flowchart representation of one variation of a methodfor patient platform or couch shuttle mode.

FIG. 5 depicts a flowchart representation of one variation of a methodfor jaw shuttle mode.

FIG. 6 depicts a flowchart representation of one variation of a methodfor updating a radiation-firing matrix (RFM) during a treatment session.

FIG. 7 depicts a flowchart representation of one variation of a methodfor dynamically updating a RFM during an emission-guided radiationtherapy session.

FIG. 8A depicts one variation of a method for radiation delivery.

FIG. 8B depicts one variation of a method where radiation delivery ismodified according to a normalization factor.

FIG. 8C depicts one variation of a pipelined normalization method.

FIGS. 9A-9D depict simulation dose-volume plots or histograms (DVH)based on one variation of a method of radiation delivery over four couchshuttle passes to a planning target region (PTV) and biological firingzone (BFZ) region. FIG. 9A depicts DVH curves after one shuttle pass,FIG. 9B depicts DVH curves after two shuttle passes, FIG. 9C depicts DVHcurves after three shuttle passes, and FIG. 9D depicts DVH curves afterfour shuttle passes.

FIG. 10 depicts one variation of a method for radiation delivery.

FIGS. 11A-11B are simulation DVH plots that depict the results of twomethods of radiation delivery over four couch shuttle passes to aplanning target region (PTV) and biological firing zone (BFZ). FIG. 11Adepicts DVH plots when negative fluence values are incorporated as partof radiation delivery.

FIG. 11B depicts DVH plots when negative fluence values are notincorporated as part of radiation delivery.

FIGS. 12A-12C depict multiple views of the planned dose distribution.FIG. 12A depicts the projection of the planned dose distribution on theIEC-Z/IEC-X plane, FIG. 12B depicts the projection of the planned dosedistribution on the IEC-Z/IEC-Y plane, and FIG. 12C depicts theprojection of the planned dose distribution on the IEC-Y/IEC-X plane.

FIGS. 13A-13C depict multiple views of the planned dose distribution.FIG. 13A depicts the projection of the delivered dose distribution onthe IEC-Z/IEC-X plane, FIG. 13B depicts the projection of the delivereddose distribution on the IEC-Z/IEC-Y plane, and FIG. 13C depicts theprojection of the delivered dose distribution on the IEC-Y/IEC-X plane.

FIGS. 14A-14C depict multiple views of the γ (gamma) metricdistribution. FIG. 14A depicts the projection of the γ (gamma) metricdistribution on the IEC-Z/IEC-X plane, FIG. 14B depicts the projectionof the γ (gamma) metric distribution on the IEC-Z/IEC-Y plane, and FIG.14C depicts the projection of the γ (gamma) metric distribution on theIEC-Y/IEC-X plane.

FIG. 14D depicts a plot that represents the cumulative fluence as afunction of beam station for a treatment session with four shuttlepasses.

FIG. 15A depicts one variation of a method of radiation delivery whenthere has been an interruption during a shuttle pass, where radiationdelivery is resumed without a new pre-scan image.

FIG. 15B depicts one variation of a method of radiation delivery whenthere has been an interruption during a shuttle pass, where radiationdelivery is resumed using a new pre-scan image.

FIG. 16 is a plot that depicts the cumulative fluence as a function ofbeam station for a treatment session with four shuttle passes, where thetreatment was interrupted at the second shuttle pass, with variousinterruption characteristics.

DETAILED DESCRIPTION

Radiation Therapy System

A radiation therapy system that may be used in shuttle mode radiationdelivery may comprise a rotatable gantry that rotates about a patienttreatment region, a therapeutic source mounted on the rotatable gantry,and a patient platform movable within or through the patient treatmentregion. The rotatable gantry may be configured to rotate 0°-360° (e.g.,a continuously rotatable gantry) or to only rotate along arc segmentsthat sweep a subset of angles (e.g., 0°-180°, 0°-270°, etc.). Oneexample of a therapeutic radiation source is a linear accelerator(linac). One or more beam-shaping elements may be disposed in the beampath of the therapeutic radiation source to define a treatment plane.For example, beam-shaping elements may comprise a jaw and a dynamicmulti-leaf collimator (MLC). The jaw may be located between thetherapeutic radiation source and the MLC, or may be located below theMLC. Alternatively, a jaw may be a split jaw where a first portion ofthe jaw is located between the therapeutic radiation source and the MLC,and a second portion of the jaw is located below the MLC and coupled tothe first portion of the jaw such that both portions move together. Thejaw may be movable within the beam of the therapeutic radiation sourcesuch that a treatment plane defined by the jaw may shift in a directionthat is parallel to the motion of the patient platform. For example, ifthe patient platform moves through the patient treatment region in theIEC-Y direction, the jaw and MLC may define a treatment plane in theIEC-XZ plane, and moving the jaw may shift the treatment plane along theIEC-Y direction. The MLC and the jaw may be separate or de-coupled suchthat shifting or moving the jaw does not move the MLC, but in othervariations, the MLC and the jaw may be coupled together such thatshifting or moving the jaw also causes a corresponding shift or movementof the MLC. Some variations of a radiation therapy system may comprise aradiation detector mounted on the gantry opposite the therapeuticradiation source. For example, some variations may comprise a MVradiation detector located opposite a linac.

Furthermore, some radiation therapy systems may comprise one or more PETdetectors, which may be mounted on the same rotatable gantry or on aseparate/second gantry that may or may not be rotatable about thepatient treatment region. Lines-of-response (LORs) defined by a pair ofcoincident 511 keV photons emitted by a positron annihilation event maybe detected by the PET detectors and transmitted to a system controller.In some variations, a patient may be injected with a PET tracer prior toa treatment session, and LORs from the PET tracer may be detected by thePET detectors. For example, the PET tracer may accumulate at patientregions with elevated metabolic rates, such as tumor regions. The systemcontroller may be in communication with all of the components of aradiation therapy system, and may, for example, generate commands to thetherapeutic radiation source, and/or gantry, and/or beam-shapingelements, and/or patient platform based on the data acquired by the PETdetectors and/or MV detector. The system controller may also compriseone or more processors that may be programmed or configured to performany of the calculations and methods described herein. The controller mayalso comprise one or more memories that may store data associated withany of the calculations and methods described herein, including, but notlimited to, imaging data (e.g., LORs data as detected by the PETdetectors), radiation delivery parameters and/or adjustment factors,machine commands, machine configurations, sensor data, and any otherdata as described herein.

One variation of a radiation therapy system is depicted in FIG. 1A. FIG.1A depicts one variation of a radiation therapy system that may be usedin shuttle mode radiation delivery. The radiation therapy system (100)may comprise a gantry (102) rotatable about a patient treatment region(104), one or more PET detectors (106) mounted on the gantry, atherapeutic radiation source (108) mounted on the gantry, a beam-shapingmodule (110) disposed in the beam path of the therapeutic radiationsource, and a patient platform (112) movable within the patienttreatment region (104). The beam-shaping module (110) may comprise amovable jaw and a dynamic multi-leaf collimator (MLC). The beam-shapingmodule may be arranged to provide variable collimation width in thelongitudinal direction of 1 cm, 2 cm or 3 cm at the system iso-center(e.g., a center of a patient treatment region). The jaw may be locatedbetween the therapeutic radiation source and the MLC, or may be locatedbelow the MLC. Alternatively, the beam-shaping module may comprise asplit jaw where a first portion of the jaw is located between thetherapeutic radiation source and the MLC, and a second portion of thejaw is located below the MLC and coupled to the first portion of the jawsuch that both portions move together. FIG. 1B is a perspectivecomponent view of the radiation therapy system (100). As shown there,the beam-shaping module may further comprise a primary collimator or jaw(107) disposed above the binary MLC (122). Optionally, the radiationtherapy system (100) may further comprise a kV CT scanner (109) on arotatable ring (111) that is attached to the rotatable gantry (102) suchthat rotating the gantry (102) also rotates the ring (111). Thetherapeutic radiation source or linac (108) and the PET detectors (106)may be mounted on the same cross-sectional plane of the gantry (i.e.,PET detectors are co-planar with a treatment plane defined by the linacand the beam-shaping module), while the kV CT scanner and ring may bemounted on a different cross-sectional plane (i.e., not co-planar withthe treatment plane).

FIG. 1C is a schematic depiction of one variation of a beam-shapingmodule comprising a split jaw (120) and a dynamic MLC (122). In thisvariation, the dynamic MLC (122) may be a binary MLC but could be anytype of MLC (e.g., a 2-D MLC). The split jaw (120) may comprise upperjaws (124) located between the therapeutic radiation source (128) (e.g.,linac) and the MLC (122), and lower jaws (126) located below the MLC(122). The upper jaws (124) and the lower jaws (126) may be coupledtogether by one or more plates (130) or frames. The jaw may be mountedon one or more curved linear rails. For example, the split jaw (120) maybe slidably mounted on one or more curved linear rails (132). The one ormore plates or frames of the split jaw may have one or more slots thatare sized and shaped to be larger than the cross-sectional size of therails such that the slots can slide over the rails (as indicated byarrow (134)). Optionally, there may be an additional rail orthogonal tothe rail (132) to provide further support to the jaw. The rails (132)are curved in this example, but they may not be curved (i.e., they maybe straight, without any curves) in other variations. The jaw may becoupled to an actuator or motor that moves the position of the jaw alongthe curved linear rail. Movement of the jaw along the rail may result ina corresponding shift of a treatment plane along the IEC-Y axis (i.e.,parallel to the axis of motion of the patient platform). In othervariations, the jaw may instead be mounted to the gantry via one or moremovable or rotatable attachment mechanisms, such as one or more hingesor pivots. The jaw may be able to move from about 0.5 cm to about 2 cmto the right or to the left of the isocenter, with a total range ofmovement (end-to-end) from about 1 cm to about 4 cm. This may correspondto a similar shift in the treatment plane, where the treatment plane mayshift along the longitudinal axis of the patient platform with a totalrange of movement of from about 1 cm to about 4 cm. It should beunderstood that the total range of movement along the longitudinal axisof the patient platform (e.g., IEC-Y) may be from about 1 cm to about 12cm, e.g., about 1 cm, about 2 cm, about 3 cm, etc. In some variations, abinary MLC may comprise 64 leaves that define an axial plane (e.g.,IEC-XZ) that are each 0.6 cm in width at iso-center leading to afield-of-view (FOV) of ˜40 cm. The jaw actuator may be configured tomove the jaw at a speed of about 0.25 cm/s to about 2 cm/s, e.g., about0.5 cm/s, about 1 cm/s, etc. In some variations, the speed of the jawmay be greater than the speed of the patient platform. While thebeam-shaping module depicted and described in FIGS. 1A-1C comprises ajaw and a MLC that are not movably attached to each other (i.e., movingor shifting the jaw does not necessarily move to shift the MLC), inother variations, the jaw and the MLC may be movable attached (i.e., thejaw and the MLC move or shift together in concert).

In some variations, the radiation therapy system may comprise a firstarray of PET detectors (106 a) and a second array of PET detectors (106b) disposed across from the first array, a linear accelerator (108) orlinac, and a beam-shaping module (110) comprising jaws and a dynamicbinary MLC. The system may further comprise a controller that is incommunication with the gantry, PET detectors, linac, and MLC, where thecontroller has one or more memories that may store treatment plans,radiation-firing matrices, fluence maps, system instructions/commands,and a processor configured to execute the calculations and methodsdescribed herein. A patient located or disposed on the patient platform(112) within the patient treatment region (104) may have been injectedwith a PET tracer that emits positrons, and the PET tracer mayaccumulate at particular regions of the patient (e.g., such as tumorregions). The annihilation of a positron with a nearby electron mayresult in the emission of two photons traveling in opposite directionsto define a LOR or positron annihilation emission path. PET detectorsmay detect one or more LORs. In some variations, the PET detectors maybe time-of-flight PET detectors, which may help to identify the locationof the positron annihilation event. A previously-calculated treatmentplan P and/or a radiation-firing matrix RFM may be updated in accordancewith data acquired by an MV detector located opposite the therapeuticradiation source, and/or the LOR data and/or PET imaging data acquiredby the PET detectors to update a treatment plan fluence map such thatthe linac and MLC leaf configuration/beamlet selection account for tumormovement. The treatment plan fluence map may be updated using LOR dataand/or PET imaging data and/or MV detector data as the patient is movedthrough the patient treatment region (e.g., in pre-defined patientplatform steps or increments, or continuous patient platform movementthrough the patient treatment region and/or treatment plane).Optionally, radiation therapy system (100) may comprise a CT imagingsystem mounted on the same gantry as the therapeutic radiation source ormounted on a separate gantry. Additional details and examples ofPET-based radiation therapy systems are described in U.S. patentapplication Ser. No. 15/814,222, filed Nov. 15, 2017 which is herebyincorporated by reference in its entirety.

The gantry (102) may be configured to rotate at a rate from about 15 RPMto about 70 RPM (e.g., about 50 RPM, about 60 RPM), the binary dynamicMLC may be configured to change leaf configurations within about 15 msor less (e.g., about 10 ms or less, about 8 ms or less), and the patientplatform (112) may be configured to move at a rate of about 0.5 mm/s orless. For example, a high-speed binary multi-leaf collimator maycomprise leaf actuating mechanisms having a spring system coupled to apneumatic system to provide sufficient motive force to move a MLC leafbetween open and closed configurations within the time constraintsdescribed above. The gantry (102) may move to (and/or across) discrete,pre-defined circumferential firing positions as it rotates. Some systemshave about 100 firing positions or angles (e.g., from about 0 degrees toabout 360 degrees, where each position is separated by a regular angularinterval).

A treatment plan may specify the radiation dose to be delivered by aradiation therapy system to each target region in a patient. The fluencemap and/or dose map of a treatment plan may be used to determine the jawposition/configuration, MLC position/configuration, gantry positionand/or motion, and the couch position and/or motion during a treatmentsession. In some variations, a radiation-firing matrix (RFM) may becalculated as part of treatment planning. A RFM may be a matrix thatdesignates the conversion from partial images (e.g., a set of LORs orincomplete image data) to a radiation beamlet pattern and/or beamletintensities to be applied to the patient during a treatment session. Forexample, in biology-guided radiation therapy such as emission-guidedradiation therapy where therapeutic radiation is applied to targetregion(s) based on detected PET LORs, RFM may be multiplied with LORdata during a treatment session to generate a fluence map that specifiesthe radiation dose to be delivered to each patient target region.Additional details regarding treatment planning methods and calculationof radiation-firing matrices are provided in U.S. Prov. Pat. Appln. No.62/537,384, filed Jul. 26, 2017, which is hereby incorporated byreference in its entirety.

Dose Modulation Artifact

Treatment plans and/or RFMs are calculated based upon images and data ofthe patient and/or target regions prior to a treatment session, oftenweeks or days before the treatment session. It is not uncommon fortarget regions, especially target regions in or in the vicinity of thelungs (e.g., lung tumors) to move during the treatment session and inparticular, to deviate from its location during treatment planning. Theirregular and/or unpredictable motion of the target region(s), inconjunction with the motion of the jaws, and/or MLC, and/or couch, maymodulate the delivered dose such that radiation is provided tonon-target tissue and/or certain areas of the target region areover-irradiated or under-irradiated (e.g., hot spots and cold spots,respectively). As the patient platform or couch advances in thetreatment region along the longitudinal direction (IEC-Y), the targetvolume is irradiated using a fan-beam (e.g., treatment plane) ofradiation as defined by the beam-shaping elements of the system.Radiation therapy systems with fast-rotating gantries (e.g., more thanabout 15 RPM, for example, about 60 RPM or about 70 RPM) and rapidbinary MLCs (e.g., with leaf transition times from about 8 ms to about15 ms) may result in a pitch (i.e., ratio of couch movement in onerotation and the collimator thickness along IEC-Y) that is less thanabout 0.3. It has been suggested that patient and couch motion alongIEC-Y (longitudinal direction) may be a significant contributor to dosemodulation artifacts.

One example of dose modulation due to tumor motion is depicted in FIGS.2A-2D. FIGS. 2A and 2B are plots that represent tumor motion (due torespiratory motion) on a radiation therapy system having a patientplatform or couch that moves at a speed of about 0.5 mm/s or less, and abinary MLC leaf size of 20 mm in the longitudinal direction (e.g.,IEC-Y), where the time to traverse the beam in the longitudinaldirection would be about 40 seconds (20 mm/[0.5 mm/s]). The time totraverse the beam may be referred to as “jaw dwell time”. While in thetransverse plane (e.g., IEC-XZ plan), the time scale for the binary MLC(e.g., leaf transition speed) is an order higher at about 0.01 secondsin a system with 100 firing positions. In this radiation therapy system,the rates of binary MLC leaf opening and closing are relatively fast ascompared to the speed of couch motion. As depicted in FIG. 2A, thedominant component of respiratory motion has a frequency of about 0.2Hz. Dose modulation due to respiratory motion and patient platformmotion can be explained as a function of the variations in the jaw dwelltime. The dose D received at any given point (y) along the longitudinalaxis (IEC-axis) in the jaw reference frame may be represented asfollows:D(y)=∫_(−t) _(ON) _(/2) ^(t) ^(ON) ^(/2) B(y−y(t))dtwhere y is the location of the beam center or the machine in thelongitudinal direction (IEC-Y) and B defines the beam profile for agiven system. y(t) is the profile of the tumor motion as seen in the jawreference frame and can be described as:y(t)=V _(couch) t+y _(breathing)(t)

The integration over time represents the averaging of the motion over acertain period of time as described in the paragraph above and is alsorepresented in FIG. 2B. Because of breathing motion, a target region(e.g., a lung tumor) may shift forward and backward, in and out of thejaw window (200), resulting in irregular dose delivery to that targetregion. The dose at a given point y may be directly proportional to thedwell time of the tumor inside the jaw window (200). The variation indwell time leads to dose modulation and dose distributionirregularities. FIG. 2C depicts a planned dose distribution (e.g., anIMRT planned dose profile) for a clinical target volume (CTV) andplanning target volume (PTV) outlined in solid black lines. The idealradiation delivery is one that delivers a homogenous dose distributionof a sufficient quantity within the boundaries of the target region.However, when the target region moves as the radiation is beingdelivered (e.g., due to patient breathing, patient platform movementthrough the treatment plane, and/or the therapeutic radiation sourcerotation about the patient), the delivered dose may deviate from theplanned distribution. FIG. 2D depicts a simulated dose distributionresulting from radiation delivery to the target region as it moves in afashion similar to the breathing motion described and depicted in FIGS.2A and 2B. As shown there, there are regions of over-irradiation (“hotspots”) (202) and regions of under-irradiation (“cold spots”) (204).

Shuttle Mode

Methods that may help to address dose modulation due to patient ortarget region motion may comprise introducing a pre-determined and knownmotion to the radiation therapy system that has a frequency componentthat is uncorrelated with the breathing motion (e.g., having a frequencycomponent that is outside of a frequency band around about 2 Hz). Onevariation of a method may comprise moving the patient platform (orcouch) and/or the beam-shaping elements (such as the jaw) in a repeatedor periodic fashion such that a patient target region(s) passes throughthe treatment plane more than once during a treatment session. Forexample, during a treatment session, the patient platform may be movedfrom a first pre-determined location to a second pre-determined locationand back to the first pre-determined location, such that the targetregion(s) cross the treatment plane at least twice. Such repeated couchmotion may be referred to as couch shuttling, where one couch shuttlecycle or pass includes moving from a first location to a second locationwhile delivering radiation from the therapeutic radiation source. Asuccessive shuttle pass may comprise moving the couch from the secondlocation back to the first location while delivering radiation from thetherapeutic radiation source. The couch may be moved continuously asradiation is delivered or may be stepped to a series of couch locationsalong the longitudinal axis (along IEC-Y) such that radiation isdelivered only when the couch is stopped at these pre-determinedlocations (or beam stations). Alternatively or additionally, during atreatment session, a jaw may be moved from a first pre-determined jawlocation to a second pre-determined jaw location (i.e., in a first jawshuttle pass) and back to the first pre-determined jaw location (i.e.,in a second jaw shuttle pass) such that the treatment plane defined atleast in part by the jaw sweeps across the target region(s) at leasttwice in the two jaw passes. Such repeated jaw motion may be referred toas jaw shuttling, where one jaw shuttle cycle or pass includes movingfrom a first jaw location to a second jaw location while deliveringradiation from the therapeutic radiation source. A successive jawshuttle pass may comprise moving the jaw from the second jaw locationback to the first jaw location while delivering radiation from thetherapeutic radiation source. The jaw opening or aperture may be keptconstant as the jaw shuttles. In other variations, the jaw opening oraperture may change while the jaw shuttles. Adjusting the speed of couchand/or jaw motion during couch and/or jaw shuttle mode may help toaddress dose modulation artifacts that arise from respiratory motion bysweeping the treatment plane over the target regions at a frequency thatis uncorrelated with the frequency peaks of respiratory motion. Forexample, shuttling the couch and/or jaw on a timescale of about 70seconds may help to mitigate artifacts that arise from breathing motionshaving a frequency peak or component on a timescale of about 5 seconds(e.g., about 0.2 Hz). FIGS. 3A and 3B are plots that represent targetregion motion over a 300 second treatment time interval or session, withone couch or jaw shuttle pass in FIG. 3A and eight couch shuttle passesin FIG. 3B. In shuttle mode, the couch or jaw comes back to the originalposition about every 70 seconds (though the couch or jaw speed may beadjusted such that the couch completes a roundtrip trajectory (i.e., apair of passes) about every 80 seconds, about every 90 seconds, aboutevery 100 seconds, etc.). As shown in the table in FIG. 3C, a treatmentsession that includes multiple shuttle cycles (e.g., 8 shuttle passes)results in a dose distribution that is closer to the planned dose than atreatment session that has a single shuttle cycle (e.g., 1 shuttlepass). The resultant dose distribution is depicted in FIG. 3E (while theplanned dose distribution is reproduced in FIG. 3D). The CTV and PTV(which together may comprise a target region or radiation-firing zone)are outlined in solid black lines. As seen there, the dose distributionin FIG. 3E is more similar to the planned dose distribution than thedose distribution in FIG. 2D.

Although couch shuttle mode and jaw shuttle mode may be describedseparately, it should be understood that both the couch and the jaw maybe shuttled simultaneously and/or sequentially during a treatmentsession (e.g., a first pass in jaw shuttle mode, a second pass in couchshuttle mode, etc.). A combination of motion between the couch and thejaws may be used to achieve the motion curve in FIG. 3B. This combinedcouch and jaw shuttle may be beneficial because it may be used tosignificantly reduce patient acceleration, particularly in cases withincreased shuttle passes. For example, the “peaks” in FIG. 3B (where theshuttling changes direction), the shuttling effect could be attained byjaw shuttling (such that most acceleration is at the jaws and theacceleration at the couch is almost zero). These methods may be usedwith radiation therapy systems that are configured for continuous couchmotion and/or step-and-shoot couch motion.

Couch Shuttle

One variation of a method for couch shuttling is represented by the flowchart diagram in FIG. 4 . The method (400) may optionally compriseloading (402) a patient on a radiation therapy system platform andacquiring (404) an image of the patient. The acquired image may be usedto register the position and location of the patient with the coordinatesystem of the radiation therapy system and/or normalize the treatmentplan before beam-on. The method (400) may comprise moving (406) thepatient platform from a first, pre-determined platform location to asecond, pre determined platform location such that all of the targetregions in the patient cross the treatment plane and are irradiated bythe therapeutic radiation source. In some variations, the therapeuticradiation source, beam-shaping module (e.g., jaws and dynamic binaryMLC), and gantry may apply a fluence to the patient based on detectedLOR data convolved or multiplied with a treatment plan RFM. Optionally,the method (400) may comprise updating (407) radiation deliveryparameters based on acquired PET data and/or MV detector data. Forexample, updating radiation delivery parameters may include normalizingthe radiation fluence derived by multiplying the acquired PET data withthe RFM, recalculating the RFM based on delivered dose or fluencecalculations, and/or updating jaw, MLC, couch and/or gantry instructionsand/or adjusting or modifying the radiation fluence for delivery usingone or more scaling factors such as one or more normalization factors,one or more dampening factors, etc. The emitted fluence and/or delivereddose (e.g., of a single shuttle pass and/or cumulatively) may optionallybe calculated. The method (400) may comprise moving (408) the patientplatform from the second pre-determined platform location to the first,pre-determined platform location while providing therapeutic radiationin the treatment plane as the target regions cross the treatment plane.The method (400) may comprise repeating (410) steps (406) and (408),with or without optional step (407), any number of times (e.g., once ormore times). In some variations, steps (406) and (408) may be repeatedan even number of shuttle cycles or times (e.g., 2, 4, 6, 8, 10 times)during the treatment session.

Jaw Shuttle

One variation of a method for jaw shuttling is represented by the flowchart diagram in FIG. 5 . The method (500) may optionally compriseloading (502) a patient on a radiation therapy system platform andacquiring (504) an image of the patient. The acquired image may be usedto register the position and location of the patient with the coordinatesystem of the radiation therapy system and/or normalize the treatmentplan before beam-on. The method (500) may comprise moving (506) thepatient platform from a first, pre-determined platform location to asecond, pre determined platform location while simultaneously moving thejaw from a first pre-determined jaw position to a second pre-determinedjaw position back to the first pre-determined jaw position n times suchthat all of the target regions in the patient cross the treatment planeand are irradiated by the therapeutic radiation source. n may be anynumber (e.g., 1, 2, 3, 4, 5, 7, 9, 11, etc.), and in some variations, nmay be an even number, for example, 2, 4, 6, 8, 10, etc., and the rateor speed at which the jaw moves may be from about 0.25 cm/s to about 2cm/s, e.g., about 0.5 cm/s, about 1 cm/s. In some variations, thetherapeutic radiation source, beam-shaping module (e.g., jaws anddynamic binary MLC), and gantry may apply a fluence to the patient basedon detected LOR data convolved or multiplied with a treatment plan RFM.While the jaw is shuttling between the first pre determined jaw positionand the second pre-determined jaw position, the configuration of the MLCmay change (i.e., the leaves may transition between the open and closedstates) in accordance with the fluence map derived from multiplying orconvolving the RFM with LOR data (e.g., based on instructions fromsegmenting the fluence map). Optionally, the method (500) may compriseupdating (507) radiation delivery parameters based on acquired PET dataand/or MV detector data. For example, updating radiation deliveryparameters may include normalization the RFM, recalculating the RFMbased on delivered dose or fluence calculations, and/or updating jaw,MLC, couch and/or gantry instructions, and/or adjusting or modifying theradiation fluence for delivery using one or more scaling factors such asone or more normalization factors, one or more dampening factors, etc.The emitted fluence and/or delivered dose (e.g., of a single shuttlepass and/or cumulatively) may optionally be calculated. The method (500)may comprise moving (508) the patient platform from the second,pre-determined platform location to the first, pre-determined platformlocation while simultaneously moving the jaw from a first pre-determinedjaw position to a second pre-determined jaw position back to the firstpre-determined jaw position n′ times such that all of the target regionsin the patient cross the treatment plane and are irradiated by thetherapeutic radiation source. n′ may be any number (e.g., n′=1, 2, 3, 4,5, 7, 9, 11, etc.) and in some variations, n′ may be an even number, forexample, 2, 4, 6, 8, 10, etc. and may or may not be the same as n. Themethod (500) may optionally comprise repeating (510) steps (506) and(508), with or without optional step (507), an even number of shuttlecycles or times (e.g., 2, 4, 6, 8, 10 times) in the treatment session.Including the optional step (510) combines both couch shuttling and jawshuttling. As described previously, the jaw may be moved at a rate fromabout 0.25 cm/s to about 2 cm/s, e.g., about 0.5 cm/s, about 1 cm/s, andthe distance between the first and second pre determined jaw positionsmay be from about 1 cm to about 4 cm, e.g., about 1 cm, about 2 cm. Thefrequency of jaw shuttling may be about 4 to about 5 times the dominantfrequency component of breathing motion.

Delivery and Interplay Artifact Mitigation

As described briefly above, radiation delivery parameters may optionallybe updated during the treatment session. Updating delivery parametersmay help to mitigate dose modulation artifacts due to patient motion. Insome variations, methods may comprise calculating the fluence deliveredto the patient during a shuttle pass (couch and/or jaw shuttle pass),comparing the delivered fluence with the treatment plan fluence andcalculating a fluence difference, and updating the RFM of a treatmentplan to deliver the fluence difference at a subsequent shuttle pass. Thefluence calculation may be a mean fluence over one or more targetregions. The fluence difference can be calculated/estimated in thestatic patient frame-of-reference, and delivered in one or moresubsequent passes without requiring any further imaging data (e.g.,without any PET imaging data, CT imaging data, or MV detector data).Alternatively, it can be calculated in the tumor point-of-view (POV)frame-of-reference. In some variations, the methods may comprisecalculating cumulative delivered fluence (and not just the fluencedelivered in a single shuttle pass) across all the previous shuttlepasses in the treatment session. Alternatively or additionally, a methodmay comprise calculating the dose delivered to the patient during ashuttle pass (couch and/or jaw shuttle pass), comparing the delivereddose with the treatment plan dose and calculating a dose difference, andupdating the RFM of a treatment plan to deliver the dose difference at asubsequent shuttle pass. The dose calculations may be a mean dose overone or more target regions. These methods may also help compensate orcorrect for dose modulation artifacts due to radiation therapy systemlimitations/constraints. System limitations/constraints may includenoise resulting from a dynamic binary MLC configuration or radiationbeam shape that does not exactly match filtered partial images (e.g.,fluence map calculated based on LOR data multiplied with the RFM), noisein the imaging system (e.g., PET, CT, MRI imaging systems), etc.Updating the RFM and/or delivery parameters (e.g., delivery fluence map,segmented machine instructions, etc.) during a treatment session basedon real-time delivery values/metrics (e.g., fluence, dose, imaging datasuch as PET LORs) may facilitate continuous artifact correction duringthe session. Regular updates to the RFM and/or delivery parameters mayhelp tune each successive radiation delivery segment (or shuttle pass)such that the cumulative delivered fluence or dose converges towards theplanned/prescribed fluence or dose delivery distribution.

FIG. 6 depicts a flowchart representation of one method for updating aRFM during a treatment session. Method (600) may comprise calculating(602) the fluence delivered to a target region after a first shuttlepass. The shuttle pass may be jaw shuttling and/or couch shuttling. Thedelivered fluence may be calculated based on therapeutic radiationsource dose chamber measurements and/or radiation beam pulse parameters(e.g., frequency, duration, duty cycle, number of pulses, etc.), and/orMLC leaf configurations, and/or jaw configurations. Optionally, thedelivered fluence may be calculated using MV detector data. The method(600) may comprise comparing (604) the delivered fluence to the targetregion (e.g., mean delivered fluence over the target region) withtreatment plan fluence to the target region (e.g., mean planned fluenceover the target region) and calculating a fluence difference Δf (e.g.,mean fluence difference over the target region), and calculating (606) anew or updated radiation-firing matrix (RFM) based on the fluencedifference Δf. After updating the RFM, the radiation therapy system maydeliver (608) the fluence difference Δf to the target region during asubsequent shuttle pass using the updated RFM. For example, inbiology-guided radiation therapy, the fluence difference Δf may bedelivered by multiplying imaging data acquired during the treatmentsession (e.g., partial images) with the updated RFM. In emission-guidedradiation therapy (a type of biology-guided radiation therapy), theupdated RFM may be multiplied with one or more detected LORs to generatea delivery fluence map. The delivery fluence map may then be segmentedinto machine instructions (e.g., MLC, linac, gantry, patientplatform/couch, and/or jaw instructions) that emit radiation to thepatient according to the fluence map. The method (600) may also be usedto update the RFM over multiple target regions. For example, the fluence(e.g., mean fluence) delivered to multiple target regions may becalculated, compared to the planned fluence (e.g., mean planned fluence)of each of the multiple target regions to calculate a difference foreach target region (Δf_(TRi) for i target regions), and the fluencedifference across all target regions may be averaged together (orotherwise normalized) to update the RFM. In some variations, the RFM maybe updated or optimized such that the fluence or dose delivery metricsare met for the greatest number of target regions. The method (600) mayalso be performed using dose calculations instead of fluencecalculations. In emission-guided radiation therapy, the method (600) maybe performed using PET or LOR data (e.g. average PET intensity over atarget region).

Pipelined Normalization

In typical radiation delivery, corrections or adjustments to thetreatment plan and/or radiation delivery parameters are applied oncebefore treatment commences. That is, corrections or adjustments based ona treatment session pre-scan image acquired are calculated once andapplied to the treatment plan and/or radiation delivery parameters oncebefore beam-on. However, because this update occurs only once at thebeginning of a treatment session, any dose modulation artifacts may notbe corrected. With the couch and/or jaw shuttle modes described herein,corrections or adjustments to the treatment plan and/or radiationdelivery parameters may be calculated and applied between shuttlepasses. On each pass, acquired data from the previous pass (e.g., PETimaging data or LORs, MV detector data, etc.) may be used to estimatethe amount of fluence or dose that has been delivered to the targetregion(s). That is, the previous imaging data may be used to predict thefuture dose in the next pass. The next shuttle pass can be corrected bythe radiation fluence or dose delivered in the treatment session up tothat point by adjusting the RFM, for example, and/or scaling or shiftingthe emitted fluence for a current shuttle pass using a normalizationfactor that may be dynamically updated based on the fluence and/or dosedelivered in the previous shuttle pass(es). This dynamic or pipelinednormalization may help to correct for errors in image noise or changesthat are detected during the delivery, including changes in theattenuation artifact from moving structures that may be outside thetarget region(s). In some variations where multiple tumor regions are tobe irradiation, a normalization factor may be calculated for eachregion, where each region-specific normalization factor may incorporatefactors and variations specific to that particular tumor region. Eachnormalization factor for each region may be calculated using any of themethods described herein. Alternatively, there may be a single, globalnormalization factor for all tumor regions.

An illustrative method for dynamically updating a RFM during anemission-guided radiation therapy session is depicted in FIG. 7 .Although these methods (as well as the other methods included herein)are described in the context of delivering radiation based on PET image(e.g., LOR) data, it should be understood that these methods may be usedfor any biology-guided radiation therapy imaging modality, including butnot limited to, radiation delivery based on CT partial image data,radiation delivery based on MRI partial image data. A method (700) mayoptionally comprise loading (702) a patient on a radiation therapysystem patient platform or couch and acquiring (704) an image of thepatient, including one or more target regions in the patient. Inemission-guided radiation therapy, a PET tracer (e.g., one thataccumulates at tumor regions) may be introduced into the patient, andthe pre-scan may be a PET image.

The method (700) may comprise calculating (706) a normalization factor(NF) based on the pre-scan image and the image used to generate thetreatment plan. The NF may be calculated by calculating the mean PETimaging signal of the pre-scan within a target region (i.e., treatmentfield or radiation-firing zone) and calculating the mean PET signal of atreatment planning image within the same target region (i.e., treatmentfield or radiation-firing zone). The NF may be a ratio of the meanplanning PET imaging signal and the mean pre-scan PET imaging signal.

Optionally, in some variations, the PET pre-scan image may be used topredict the dose or fluence that will be delivered in a shuttle passthat immediately follows the pre-scan. For example, the pre-scan imagecan be used to predict or estimate the real-time fluence or dose thatwill be delivered will meet certain delivery metrics. The pre-scan imagecan be normalized by the NF. The pre-scan image can now be used toestimate the dose of radiation delivery and may be significantly lesssensitive to image noise of the PET image. The normalization factor canalso be used to normalize the mean treatment plan fluence or meantreatment plan radiation dose to the target region.

Method (700) may comprise adjusting (708) the treatment plan RFM basedon the calculated NF. Adjusting the RFM by the NF may comprise modifyingthe RFM using any linear operation or transformation based on the NF.Examples of linear operations may including multiplying, convolving,and/or scaling the RFM by the NF. In some variations, it may alsoinclude adding or subtracting a constant based on the NF to the RFM.Method (700) may then comprise moving (710) the patient platform from afirst, pre-determined platform location to a second, pre determinedplatform location (i.e., a first couch shuttle pass) and back to thefirst, pre-determined platform location (i.e., a second couch shuttlepass) such that all of the target regions in the patient intersect thetreatment plane at least once (e.g., one or more times, two or moretimes, etc.). While moving the patient platform, the target regions maybe irradiated based on the adjusted RFM and PET LOR data acquired by thePET detectors. When the patient platform has returned to the firstpre-determined platform location, the NF may be updated (712) based onthe fluence and/or dose delivered during the shuttle pass. In somevariations, the NF may be updated based on the PET LOR data acquiredduring the shuttle pass. For example, the updated NF may be calculatedby taking the ratio of the planned fluence (e.g., mean planned fluence)to a target region (e.g., treatment field, radiation-firing zone) to theactual delivered fluence (e.g., mean delivered fluence) to that targetregion. Alternatively or additionally, the updated NF may be calculatedby taking the ratio of the planned dose (e.g., mean planned dose) to atarget region (e.g., treatment field, radiation-firing zone) to theactual delivered dose (e.g., mean delivered dose) to that target region,where the delivered dose is calculated based on the delivered fluenceand the pre-scan image or treatment planning image. Updating the NFbased on fluence calculations may help radiation delivery to meetfluence-based metrics, such as total conservation of monitor units,while updating the NF based on dose calculations may help radiationdelivery to meet dose-based metrics (e.g., D95 coverage, max OAR dose).In emission-guided radiation therapy, the NF may be updated based on PETintensity over a target region (e.g., ratio of the mean PET intensity ofa target region based on a PET planning or pre-scan image to the meanPET intensity of the target region based on LOR data acquired during thetreatment session). The RFM may be updated using any linear operation ortransformation based on the NF, as described above. Optionally, method(700) may comprise repeating (714) steps (710), (712) any number oftimes during a treatment session, and in some variations, an even numberof times during a treatment session, and may stop when the deliveredfluence or dose converges to the planned fluence or dose.

While method (700) provides an example of dynamic normalization usingpatient platform or couch shuttling, it should be understood that themethod (700) may also be used in jaw shuttling mode, where the NF andRFM are updated after each jaw shuttle pass. In jaw shuttle mode, it maybe that the patient platform completes only one pass during thetreatment session, since the jaw has completed multiple shuttle passesover the single platform shuttle pass. Alternatively or additionally,method (700) may be used in a combined couch and jaw shuttling mode.

In some variations, a method for radiation delivery may compriseadjusting the radiation fluence or dose to be emitted or delivered usingone or more adjustment factors such as one or more of normalizationfactors, dampening factors, weighting factors, and the like. Theradiation fluence or dose to be emitted or delivered during a particularshuttle pass (e.g., couch/platform shuttle and/or jaw shuttle) may bescaled and/or shifted by the adjustment factor(s). In some variations,the adjustment factor(s) may be adjusted and/or updated for each shuttlepass so that the adjustment factor(s) may reflect the up-to-date stateof the patient (e.g., using imaging data, and/or images, and/or otherphysiological data) as well as the radiation delivered during thetreatment session. For example, the adjustment factor(s) may be updatedor tuned based on the radiation fluence emitted or dose delivered duringthe previous shuttle pass and the amount of fluence or dose asprescribed by the treatment plan. In one variation, the fluence (ordose) to be delivered in a shuttle pass may be scaled by a normalizationfactor (and/or optionally, a dampening factor) that may be calculatedbased at least in part on the radiation delivered in the previousshuttle pass and imaging data acquired during the previous shuttle pass(and/or any other imaging data acquired during the treatment session).Scaling the radiation fluence or dose by a normalization factor that isadjusted for each shuttle pass may facilitate the convergence of thecumulative radiation delivered toward the planned radiation fluence ordose (i.e., radiation fluence or dose specified by the treatment plan).In the case of emission-guided radiation therapy where the radiationfluence or dose applied to a patient is calculated based on imaging data(e.g., PET imaging data) acquired during the treatment session, scalingor otherwise adjusting the radiation fluence or dose with anormalization factor that accounts for the cumulative fluence or dosethat has already been delivered during the session and the differencebetween the quantity of delivered radiation and the planned quantity ofradiation (e.g., as specified by a treatment plan and/or clinician) mayhelp compensate for any radiation delivery errors, fluctuations and/orunexpected or unintended variations due to tumor motion, patient motion,and/or variable tracer uptake, and the like. While the methods includedherein are described in the context of emission-guided orbiologically-guided radiotherapy using PET tracers and positron emissiondata, it should be understand that these methods may also be used in anyradiotherapy modality that applies radiation using data acquired inreal-time during a treatment session. In addition, the methods describedherein for the calculation of one or more normalization factors may useradiation fluence, the methods may alternatively or additionally useradiation dose to calculate normalization factors. A radiation dosevalue or profile may be derived from a fluence value or profile using adose calculation matrix A, where matrix A may be a linear operator thatmaps fluence to dose in the image space. Specific reference to aradiation fluence or dose in any of the methods described herein mayrefer more generally to a quantity of radiation that is emitted ordelivered to a target region.

Optionally, for any of the methods described herein, the treatment timeand/or number of couch shuttle passes N may be selected before radiationdelivery (though these methods may also be adapted for use with jawshuttling). The treatment times and/or number of shuttle passes N may bedetermined or selected, for example, during treatment planning, before apatient is set up for a treatment session, or after the patient is setup for treatment but before the treatment beam is activated. Optionally,a dampening factor α (from which a normalized dampening factor β may bederived) may be selected according to a desired radiation delivery rateacross multiple shuttle passes. Given the number of shuttle passes N anda dampening factor α, normalized dampening factor β may be derived asfollows:

$\beta_{i} = \frac{\alpha^{i - 1}}{\sum_{j = 1}^{N}\alpha^{j - 1}}$

For example, in some variations, a dampening factor α may be selectedsuch that a larger proportion of the prescribed or planned radiationfluence or dose is delivered in the earlier shuttle passes than in thelatter shuttle passes (i.e., the radiation fluence emitted in a firstpass is greater than the radiation fluence emitted in the last pass). Insuch manner, the earlier shuttle passes function to deliver the majorityof the planned radiation dose, while the later shuttle passes functionto deliver fluence corrections or adjustments to compensate for anyerrors, artifacts, and/or motion (e.g., interplay artifacts, patient ortumor motion) that may have occurred during a treatment session. In anyof the methods included herein, the dampening factor α may be from 0 toabout 1, e.g., about 0.5, 0.6, 0.7, 0.75, 0.77, 0.8, 0.83, 0.85, 0.90,0.91, 0.97, 1, etc. In addition to specifying the number of shuttlepasses N, the treatment session duration time may also be specified. Insome variations, the treatment session duration may be held constant andthe time spent per shuttle pass may be adjusted according to the numberof shuttle passes. That is, as the number of shuttle passes increases,the time per shuttle pass may decrease, and the dwell time of the targetregion in the therapeutic radiation beam plane for a particular shuttlepass may be reduced. The cumulative dwell time across the entiretreatment session (e.g., across all N shuttle passes) may remainapproximately constant regardless of the number of shuttle passes, sincethe dwell time is reduced accordingly. In the examples described herein,the number of shuttle passes N may be four and the dampening factor αmay be 0.83 (i.e., 1/1.2), but N and α (and subsequently, β) may vary asdesired. For example, in a treatment session where N=4 and α=(1/1.2) or0.8333, the normalized dampening factor for each of the four passes maybe β₁=0.33, β₂=0.28, β₃=0.23, β₄=0.19. While a normalization factor andone or more dampening factors (α, β) may be used to adjust the radiationfluence emitted to a target region during a shuttle pass, the radiationfluence may be adjusted with only a normalization factor, a plurality ofnormalization factors, a single dampening factor, and/or any otheradditional factors that tune the emitted radiation to reflect thepatient and/or system conditions during the treatment session.

FIG. 8A depicts one variation of a method where the radiation appliedduring a treatment session is adjusted for each shuttle pass. Asdescribed previously, a shuttle pass may comprise moving a patientplatform or couch from a first location to a second location such thatthe one or more tumor regions in a patient pass through a therapeuticradiation beam plane once. The couch may be moved continuously asradiation is delivered (e.g., helical radiation delivery), or may bemoved in steps such that radiation is delivered only when the couch isstopped at a predetermined couch location or step (e.g., beam stationdelivery, therapeutic radiation beam is stopped while the couch ismoving and on when the couch is stopped). While the methods describedbelow are in the context of couch shuttling, it should be understoodthat similar methods may be adapted for use in jaw shuttling. Method(800) may comprise moving (802) a patient (i.e., by moving a patientplatform) from a first location to a second location such that thepatient passes through a radiation treatment plane while acquiringimaging data, and applying (804) a first quantity of radiation as thepatient passes through the radiation beam plane. This may be referred toas a first shuttle pass, and the first quantity of radiation may bedetermined at least in part based on the treatment plan, the imagingdata acquired during the first pass (e.g., full images such as apre-scan image of the patient X_(prescan) acquired at the start of atreatment session, and/or partial images, such as one or more LORs orpositron annihilation emission paths), along with one or more adjustmentfactors (e.g., a first normalization factor and/or a first dampeningfactor). Method (800) may then comprise moving (806) the patient (i.e.,by moving the patient platform) from the second location to the firstlocation such that the patient passes through a radiation treatmentplane while acquiring imaging data, and applying (808) a second quantityof radiation as the patient passes through the radiation beam plane,where the second quantity of radiation is different from the firstquantity of radiation. This may be referred to as a second shuttle pass,and the second quantity of radiation may be determined at least in partbased on the treatment plan, the imaging data acquired during the secondpass (e.g., full images such as a pre-scan image of the patientX_(prescan) acquired at the start of a treatment session, and/or partialimages, such as one or more LORs or positron annihilation emissionpaths), along with one or more adjustment factors (e.g., a secondnormalization factor and/or a second dampening factor) as well as thequantity of radiation that was delivered in the previous (first) pass.The second normalization factor and/or second dampening factor may bedifferent from the first normalization factor and/or first dampeningfactor. The steps (802-804) and/or (806-808) may be repeated as manytimes as desired or as specified (e.g., up to N shuttle passes). Thenumber of shuttle passes N may be odd or even, and therapeutic radiationmay be applied as the patient is alternately shuttled between the firstand second locations. In some variations, the distance between the firstlocation and the second location may span a substantial length of thepatient's body and may be, for example, at least as long as the distancebetween the target regions that are furthest from each other (i.e.,along the longitudinal, IEC-Y axis) or at least as long as the largestdimension of a single target region (i.e., the length of a target regionalong the longitudinal, IEC-Y axis).

In some variations where radiation delivered to target regions may be atleast partially determined by imaging data (and/or any patient or systemdata) acquired during the treatment session, the fluence emitted by theradiation therapy system may be adjusted to help ensure thatcumulatively, the delivered dose converges to the prescribed dose (i.e.,dose specified by the treatment plan or D_(plan). The adjustment factorfor a particular shuttle pass may be derived based on the acquiredimaging data (and/or patient or system data), the amount of radiationthat has been delivered already, treatment plan parameters, and/or anyother filters or scaling or weighting factors, and the adjustment factormay be calculated and/or updated for each shuttle pass.

FIG. 8B depicts one variation of a method where the radiation appliedduring a shuttle pass is modified or adjusted according to anormalization factor that is calculated before the shuttle pass beginsand the normalization factor is updated for each shuttle pass (i.e.,pipelined normalization). The method (820) may comprise calculating(822) a normalization factor k_(i), applying (824) an i^(th) pass ofradiation while acquiring imaging data, where the emitted radiationfluence is calculated based on the acquired imaging data and thecalculated normalization factor k_(i), calculating (826) a normalizationfactor k_(i+1), applying (828) an i^(th) pass of radiation whileacquiring imaging data, where the emitted radiation fluence iscalculated based on the acquired imaging data and the calculatednormalization factor k_(i+1), and repeating (830) the calculation of thenormalization factor and the application of radiation (826-828) for i=1,. . . , N number of radiation delivery passes. In one variation, thenormalization factor k_(i+1) may be calculated by taking the differencebetween the cumulative planned radiation fluence or dose D_(plan) andthe radiation fluence that has been delivered so far (i.e., in allprevious shuttle passes) and normalizing (e.g., dividing) the differencebetween the planned and delivered fluence with predicted cumulativefluence (which may not be segmented into discrete fluence values orlevels) that would be applied to the target region if each of the futureshuttle passes delivered the same amount of radiation as was deliveredin the previous shuttle pass. The radiation cumulatively emitted duringthe previous shuttle passes may be calculated based on radiation therapysystem commands and configurations (e.g., pulse parameters from thetherapeutic radiation source, MLC configurations, gantry rotations,etc.) and/or sensor data (e.g., MV detector data, dose chamber data,position sensor data from the MLC, couch, gantry, etc.), and/or imagingdata (e.g., PET data, CT data, MRI data, etc.). In emission-guidedradiation therapy (e.g., biologically-guided radiation therapy) whereimaging data comprises positron annihilation emission data (i.e., LORdata), the radiation emitted by the radiation therapy system may becalculated by multiplying acquired PET emission data (x_(i)) with theRFM from the treatment planning system, masked with a spatial filter(BFZ) that limits the radiation delivery to the target region (i.e.,biological firing zone) and optionally scaled with one or morenormalization (k_(i)) and/or dampening factors (β_(i)). The acquired PETemission data (x_(i)) may comprise one or more LORs, but may not includea sufficient number of LORs for the generation of a complete or full PETimage. For other radiation therapy systems, imaging data may comprise2-D projection X-ray images (for a CT imaging system) or MRIsub-samplings in k-space (for a MRI imaging system). The normalizationfactor for the first shuttle pass (k₁) may be calculated based on apre-scan image (X_(prescan)) of the patient acquired at the start of atreatment session.

In one variation, a normalization factor for a shuttle pass index i(where i=1, 2, . . . , N shuttle passes) may be calculated as follows:

$k_{i} = \left\{ \begin{matrix}\frac{D_{plan}}{D_{0,{raw}}} & {{{for}i} = 1} \\\frac{D_{plan} - {\sum_{j = 1}^{i - 1}{k_{j}\beta_{j}D_{j,{raw}}}}}{\sum_{j = i}^{N}{\beta_{j}D_{{i - 1},{raw}}}} & {{{for}2} \leq i \leq N}\end{matrix} \right.$where D_(plan) is the radiation dose or fluence as specified in thetreatment plan, β_(i) is a dampening factor, and D_(i,raw) is theradiation fluence delivered (or to-be-delivered) for a shuttle pass i inaccordance with the treatment plan without any adjustment based onreal-time treatment session data. D_(i,raw) may be a calculatedradiation fluence (e.g., with continuous fluence values) or a segmentedradiation fluence (e.g., with discrete fluence values or levels), wherea segmented radiation fluence may comprise fluence values that representthe fluence values deliverable by a radiation therapy system. In somevariations, for radiation delivery based on imaging data acquired duringa treatment session,

${D_{0,{raw}} = \left( {D_{prescan} \times \frac{{treatment}{time}}{{prescan}{time}}} \right)},{where}$D_(prescan) = A × (X_(prescan) * RFM) ∘ BFZwhere A is a dose calculation matrix generated based on radiationtherapy system parameters that maps fluence to dose in the image space,X_(prescan) is an image (e.g., a full image such as a full PET image, afull CT image, and/or a full MRI image) acquired at the beginning of atreatment session before any therapeutic radiation is delivered, RFM isa radiation-firing matrix generated by the treatment planning systemthat designates the conversion from image data (e.g., partial images,such as a set of LORs or 2-D X-ray projections or MRI sub-samplings ink-space, or incomplete image data) to a radiation beamlet pattern and/orbeamlet intensities, and BFZ is a spatial filter comprising a bitmapthat specifies the target region while masking out non-target regions.“Treatment time” is the total treatment delivery time defined by thetreatment planning system, which may be selected or determined by aclinician or user, and “prescan time” is the total time spend acquiringthe pre-scan image X_(prescan).

The term Σ_(j=i) ^(N)β_(j)D_(i−1,raw) may represent the predictedcumulative fluence that would be applied to the target region if each ofthe future shuttle passes delivered the same amount of radiation as wasdelivered in the previous shuttle pass and may also be referred to asD_(i,predicted cumulative) (which may not be segmented into fluencelevels or values deliverable by a radiation therapy system). In somevariations, D_(i,predicted cumulative) may be expressed as:

$D_{i,{{predicted}{cumulative}}} = {{\overset{N}{\sum\limits_{j = {i + 1}}}{\beta_{j - 1}D_{{i - 1},{raw}}}} = {\overset{N}{\sum\limits_{j = {i + 1}}}{\beta_{j - 1}\left\lbrack {\left( {x_{i}*{RFM}} \right) \circ {BFZ}} \right\rbrack}}}$

For shuttle passes following the first shuttle pass (2<=i<=N), thenormalization factor k_(i) may also be written as follows:

${k_{i} = \frac{D_{plan} - {\sum_{j = 1}^{i - 1}{k_{j}{\beta_{j}\left\lbrack {\left( {x_{j}*{RFM}} \right) \circ {BFZ}} \right\rbrack}}}}{\sum_{j = i}^{N}{\beta_{j}\left\lbrack {\left( {x_{i - 1}*{RFM}} \right) \circ {BFZ}} \right\rbrack}}},{{{for}2} \leq i \leq N}$

Where x_(i) represents the imaging data acquired during shuttle pass i.In method (820), steps (822) and (826) may calculate the normalizationfactors k_(i), and k_(i+1) as described above.

The radiation fluence delivered in an i^(th) shuttle pass (D_(i,calc))may be calculated as follows:

D_(i, calc) = k_(i)β_(i)D_(i, raw) = k_(i)β_(i)[(x_(i) * RFM) ∘ BFZ]

When applied to method (820), the radiation fluence emitted in (824) maybe k_(i)β_(i) [(x_(i)*RFM)∘BFZ] and the radiation fluence emitted in(828) may be k_(i+1)β_(i+1) [(x_(i+1)*RFM)∘BFZ], where x_(i), x_(i+1)represent imaging data acquired during shuttle passes i and i+1,respectively.

FIG. 8C depicts one variation of a pipelined normalization method wherethe radiation applied during a shuttle pass is modified or adjustedaccording to a normalization factor that is calculated based on themost-recently acquired imaging data (e.g., partial and/or full images).Method (840) may be used with any image-guided or emission-guided (e.g.,biologically-guided) radiotherapy where imaging data and/or patient dataand/or system data is acquired during the radiation therapy session andused to adapt, modify or otherwise adjust radiation delivery. While theflowchart of FIG. 8C depicts the method applied to a first shuttle passand to a second shuttle pass of radiation delivery, it should beunderstood that the method may also be extended for additional shuttlepasses, as may be desired. Method (840) may optionally comprise loading(842) a patient on radiation therapy system platform, acquiring (844) animage of the patient (e.g., a pre-scan PET and/or CT image X_(prescan)),optionally selecting (846) the number of passes (N) and dampening factor(a) and calculating normalized dampening factor (β_(i)) for each pass(β₁, β₂, . . . , β_(N)), calculating (848) a first normalization factork₁ based on the pre-scan image X_(prescan), and applying (850) a firstpass of radiation while acquiring imaging data x₁, where the emittedradiation fluence D_(1,calc) is calculated based on the acquired imagingdata and the normalization factor k₁. The number of passes and thecalculation of the dampening factor for each of the shuttle passes maybe calculated as described previously and at any time before thetreatment session, for example, during treatment planning, beforepatient set up, and/or before the therapeutic radiation source isactivated (i.e., beam on), and this step may be included in any of theother methods described herein. In this example, the normalizationfactor k₁ may be calculated or determined as follows:

$k_{1} = {\frac{D_{plan}}{D_{0,{raw}}}{where}}$${D_{0,{raw}} = \left( {D_{prescan} \times \frac{{treatment}{time}}{{prescan}{time}}} \right)},{where}$D_(prescan) = A × (X_(prescan) * RFM) ∘ BFZ

Where the dose calculation matrix A, radiation-firing matrix RFM, andbiological firing zone bitmask BFZ are as described previously. Theradiation applied in the first pass to a target region (e.g., abiological firing zone or radiation firing zone) based on the acquiredimaging data may be calculated as follows:D _(1,calc) =k ₁β₁ D _(1,raw) =k ₁β₁[(x ₁*RFM)∘BFZ]

The image data x₁ acquired during the first shuttle pass may be partialimages, for example, comprising one or more LORs (for image dataacquired with PET detectors), one or more 2-D projection X-ray images(for image data acquired with CT detectors), and/or sub-samplings ink-space (for image data acquired with MRI detectors). While thetreatment plan parameters (e.g., RFM, BFZ) may designate the delivery ofa radiation fluence D_(1,raw) to the target region, the normalizationfactor and dampening factor may adjust (i.e., scale or normalize)D_(1,raw) to reflect the real-time treatment conditions during thesession and/or compensate for variations and/or artifacts in the imagingdata x₁ acquired during the first shuttle pass. D_(1,raw) may be acalculated radiation fluence (e.g., with continuous fluence values) or asegmented radiation fluence (e.g., with discrete fluence values orlevels), where a segmented radiation fluence may comprise fluence valuesthat represent the fluence values deliverable by a radiation therapysystem.

Method (840) may further comprise calculating (852) a predictedcumulative fluence (D_(1,predicted cumulative)) based on the imagingdata acquired during the first pass by summing over N passes,calculating (854) a normalization factor k₂ for the second pass ofradiation delivery where k₂ is calculated by calculating the differencebetween D_(plan) and the total fluence emitted in the first pass, andtaking the ratio of the difference over the predicted cumulativefluence, and applying (856) a second pass of radiation while acquiringimaging data, where the emitted radiation fluence D_(2,calc) iscalculated based on the acquired imaging data and the normalizationfactor k₂. The predicted cumulative fluence may be calculated (852)based on the imaging data acquired during the first shuttle pass:

$D_{1,{{predicted}{cumulative}}} = {{\overset{N}{\sum\limits_{j = 2}}{\beta_{j}D_{1,{raw}}}} = {\overset{N}{\sum\limits_{j = 2}}{\beta_{j}\left\lbrack {\left( {x_{1}*{RFM}} \right) \circ {BFZ}} \right\rbrack}}}$

The normalization factor k₂ for the second shuttle pass may becalculated (854) by taking the difference between the planned radiationfluence or dose and the fluence emitted in the first shuttle pass,normalized over the predicted cumulative fluence:

$k_{2} = {\frac{D_{plan} - D_{1,{calc}}}{D_{1,{{predicted}{cumulative}}}} = \frac{D_{plan} - {k_{1}\beta_{1}D_{1,{raw}}}}{\sum_{j = 2}^{N}{\beta_{j}D_{1,{raw}}}}}$

Accordingly, the radiation applied in the second shuttle pass to thetarget region (e.g., a biological firing zone or radiation firing zone)based on the acquired imaging data during the second shuttle pass may becalculated as follows:D _(2,calc) =k ₂β₂ D _(2,raw) =k ₂β₂[(x ₂*RFM)∘BFZ]

Where image data x₂ acquired during the second shuttle pass may bepartial images, for example, comprising one or more LORs (for image dataacquired with PET detectors), one or more 2-D projection X-ray images(for image data acquired with CT detectors), and/or sub-samplings ink-space (for image data acquired with MRI detectors), as describedpreviously and throughout. D_(2,raw) may be a calculated radiationfluence (e.g., with continuous fluence values) or a segmented radiationfluence (e.g., with discrete fluence values or levels), where asegmented radiation fluence may comprise fluence values that representthe fluence values deliverable by a radiation therapy system.

In some variations, the normalization factor for the first shuttle passmay be calculated using dose values derived from the pre-scan image,while the normalization factors for the successive shuttle passes may becalculated using fluence values (optionally be segmented fluence values,including any fluence segmentation errors). Dose calculations may bemore computationally-intensive than fluence calculations (since fluencemay be calculated by multiplying the image data with theradiation-firing matrix, while dose calculations may involve anadditional multiplication with a dose calculation matrix), and it maytherefore be preferable for some radiation therapy systems to calculatenormalization factors during a treatment session using radiation fluenceinstead of radiation dose so that the latency between the acquisition ofimaging data and the application of radiation is reduced. Since thefirst normalization factor is calculated before therapeutic beam-on, aradiation therapy system may be computationally available forcalculating the first normalization factor based on the dose valuesderived from the pre-scan image. Some variations of radiation therapysystems may comprise one or more processors with greater computationalpower, in which case, the normalization factors may be calculated usingdose values derived from the imaging data acquired during the treatmentsession. Alternatively or additionally, all normalization factors may becalculated on fluence values derived from image data acquired during thetreatment session.

FIGS. 9A-9D are simulation dose-volume plots or histograms (DVH) thatdepict a method of radiation delivery over four couch shuttle passes toa planning target region (PTV) and biological firing zone (BFZ) regionusing one or more of the pipelined normalization methods describedherein. The BFZ region includes the PTV and a margin around the PTV.FIG. 9A depicts the DVH curves after a first shuttle pass. The plannedDVH for the PTV is represented by line (903), with the maximum DVH bound(i.e., upper threshold acceptable for treatment) represented by line(905) and the minimum DVH bound (i.e., lower threshold acceptable fortreatment) represented by line (907). The predicted delivered dose tothe PTV is represented by the delivered DVH line (901). Similarly, andthe planned DVH for the BFZ region is represented by line (904), withthe maximum DVH bound (i.e., upper threshold acceptable for treatment)represented by line (906) and the minimum DVH bound (i.e., lowerthreshold acceptable for treatment) represented by line (908). Thepredicted delivered dose to the BFZ region is represented by thedelivered DVH line (902). After the first shuttle pass, the predictedDVH curve for the PTV (901) exceeds the planned DVH curve for the PTV(905), and falls out of range of the maximum DVH bound (905). Similarly,the predicted DVH curve for the BFZ region (902) exceeds the planned DVHcurve for the BFZ region (904), and falls out of range of the maximumDVH bound (906). As the radiation delivered to the PTV and the BFZregion builds up over multiple shuttle passes, with FIG. 9B depictingthe same DVH curves as in FIG. 9A after a second shuttle pass, with FIG.9C depicting the DVH curves after a third shuttle pass, and with FIG. 9Ddepicting the DVH curves after a fourth shuttle pass, it may be seen howthe delivered DVH curves (PTV DVH 909 and BFZ region DVH 910) convergestoward the planned DVH curves (PTV DVH 903 and BFZ region DVH 904)and/or remain within the bounds defined by the maximum and minimum DVHcurves for the PTV and BFZ regions, respectively.

Pipelined Normalization with Negative Fluence Values

In some variations, when calculating the radiation fluence for delivery,the calculated D_(i,raw)=[(x_(i)*RFM)∘BFZ] value may result in anegative radiation fluence value. A negative radiation fluence value maynot be deliverable by the radiation therapy system in the same shuttlepass, however, if such negative fluence values are zeroed out and/orignored, the cumulative delivered radiation may deviate substantiallyfrom the planned fluence or dose values. One variation of a method forhandling negative fluence values accrued in one shuttle pass maycomprise incorporating the negative fluence values into the next shuttlepass, where they may be combined with non-negative fluence values. Thenext fluence values may be positive and therefore, deliverable in one ormore later shuttle passes. In some variations, the negative fluencevalues in one shuttle pass may be incorporated in the calculation of thepredicted cumulative fluence that would be delivered over the remainingshuttle passes, and used to normalize the difference between D_(plan)and D_(i,calc)(i.e., total cumulative delivered radiation in thetreatment session up until the next shuttle pass). FIG. 10 depicts onevariation of a method where the radiation applied during a shuttle passis modified or adjusted according to a normalization factor that iscalculated before the shuttle pass begins, and incorporates negativefluence values encountered during radiation delivery in the previouspass. Method (1000) may comprise applying (1002) an i^(th) pass ofradiation while acquiring imaging data where the emitted radiationfluence is calculated based on the acquired imaging data and acalculated normalization factor k_(i), calculating (1004) a predictedcumulative fluence based on the imaging data acquired during the firstpass, including negative fluence values (if any), by summing over Npasses, calculating (1006) a normalization factor k_(i+1) for the nextpass, based on the predicted cumulative fluence, and applying (1008) an(i+1)^(th) pass of radiation while acquiring imaging data where theemitted radiation fluence is calculated based on the acquired imagingdata and the calculated normalization factor k_(i+1). Optionally, method(1000) may further comprise repeating the calculation of thenormalization factor and the application of radiation (1004-1008) fori=1, . . . , N. The predicted cumulative fluence may incorporatenegative fluence values as follows:

$D_{i,{{predicted}{cumulative}}} = {\overset{N}{\sum\limits_{j = i}}{\beta_{j}\left( {D_{{i - 1},{raw}} - D_{{i - 1},{raw}}^{Negative}} \right)}}$

By incorporating the negative fluence value into theD_(i, predicted cumulative), such negative fluence is accounted for inthe generation of k_(i) for the next shuttle pass, sinceD_(i, predicted cumulative) is used to normalize the difference betweenthe planned radiation fluence and the delivered radiation fluence.

FIGS. 11A-11B are simulation DVH plots that depict the results of twomethods of radiation delivery over four couch shuttle passes to aplanning target region (PTV) and biological firing zone (BFZ). FIG. 11Adepicts the result of radiation delivery to a PTV and BFZ region (aspreviously described) when negative fluence values are incorporated inthe predicted cumulative fluence values and included in the calculationof the normalization factor k. The planned DVH curve for the PTV isrepresented by line (1101), with the maximum DVH curve represented byline (1103) and the minimum DVH curve represented by line (1105). Thedelivered DVH curve for the PTV is represented by line (1107), and asseen along the falling edge of the DVH curve, the delivered DVH curvefor the PTV is located within the minimum and maximum DVH boundaries.Similarly, for the BFZ region, the planned DVH curve for the BFZ regionis represented by line (1102), with the maximum DVH curve represented byline (1104) and the minimum DVH curve represented by line (1106). Thedelivered DVH curve for the BFZ region is represented by line (1108),and as seen along the falling edge of the DVH curve, the delivered DVHcurve for the BFZ is located within the minimum and maximum DVHboundaries. In contrast, FIG. 11B depicts the result of radiationdelivery to a PTV and BFZ region (as previously described) when negativefluence values are ignored. The planned DVH curve for the PTV isrepresented by line (1101′), with the maximum DVH curve represented byline (1103′) and the minimum DVH curve represented by line (1105′). Thedelivered DVH curve for the PTV is represented by line (1107′), and asseen in the plot, the delivered DVH curve for the PTV is not locatedwithin the boundaries defined by the minimum and maximum DVH curves.Similarly, for the BFZ region, the planned DVH curve for the BFZ regionis represented by line (1102′), with the maximum DVH curve representedby line (1104′) and the minimum DVH curve represented by line (1106′).The delivered DVH curve for the BFZ region is represented by line(1108′), and as seen in the plot, the delivered DVH curve for the BFZ isnot located within the boundaries defined by the minimum and maximum DVHcurves. Including negative fluence values in the calculation of anormalization factor may be incorporated in any of the methods describedherein.

The pipelined normalization methods for radiation delivery describedherein may use the mean of the planned fluence (or dose) to constrainthe mean of the delivered fluence (or dose). This may help the radiationtherapy system to deliver radiation having a mean fluence that convergesto the mean planned fluence, which may help to address motion and/orimaging artifacts encountered during the treatment session. FIGS.12A-12C, 13A-C, and 14A-C depict multiple views of the planned dosedistribution, delivered dose distribution over four shuttle passes, andthe γ metric, respectively, from multiple planes. The γ (gamma) metricmay be calculated as the square root of the squared sum of distance toagreement (DTA) and percentage dose difference (DD) between two dosedistributions. One of the dose distribution may be defined as referencedose distribution (typically the ground truth) and the other one may bedefined as evaluated dose distribution. The established values for DTAmay be 3 mm and DD may be 3%. The gamma metric may be first calculatedfor all pair of voxels in the two dose distributions and a passing valuemay be defined as value of gamma<=1 and fail may be defined as value ofgamma>1. The gamma passing rate may be calculated as the percentage ofvoxels in the treatment volume that pass the gamma evaluation. Thetreatment volume may typically be defined as the voxels in the referencedose distribution that receive more than 10% of the prescribed dose.FIGS. 12A, 13A, and 14A depict the projection of the dose distributionon the IEC-Z/IEC-X plane (i.e., the plane orthogonal to the direction ofcouch motion), FIGS. 12B, 13B, and 14B depict the projection of the dosedistribution on the IEC-Z/IEC-Y plane, and FIGS. 12C, 13C, and 14Cdepict the projection of the dose distribution on the IEC-Y/IEC-X plane(i.e., the plane orthogonal to the treatment beam, “beam's eye view”).As may be seen in FIGS. 14A-C the γ metric passing rate (i.e., gammavalue less than or equal to one) is over 99% when radiation deliverybased on imaging data acquired during the treatment session is adjustedor modified with a normalization factor generated using one or more ofthe methods described herein. Regions where the gamma metric exceed one(as indicated by arrows (1400)) make up less than 1% of the totaldistribution depicted in FIGS. 14A-14C. FIG. 14D is a plot that depictsthe cumulative fluence as a function of beam station for a treatmentsession with four shuttle passes. Each of the prediction passes arecalculated as the sum of predicted fluence for remaining passes anddelivered fluence. The delivered is the final fluence that is deliveredto the tumor site. Each beam station is a predetermined couch locationor step along the IEC-Y axis where the couch may be stopped while thetherapeutic radiation beam is activated and applying radiation to thepatient. The therapeutic radiation beam is off (i.e., not activated)while the couch is moving between beam stations. The line with thesquare-shaped bullets represents the planned fluence and the line withthe cross-shaped bullets represents the fluence delivered after fourshuttle passes. As depicted there, the mean delivered cumulative fluenceconverges toward the mean of the planned fluence with each additionalshuttle pass. While the examples described herein comprise applyingradiation over four shuttle passes, it should be understood that thenumber of shuttle passes over a treatment session may vary, and may befrom 2 shuttle passes to 100 shuttle passes, e.g., 4 shuttle passes, 6shuttle passes, 7 shuttle passes, 8 shuttle passes, 10 shuttle passes,12 shuttle passes, etc.

Treatment Interruption

If a treatment session is not completed or interrupted (e.g., due topatient discomfort or illness, system component malfunction, etc.), a“make-up” fraction may be performed. A make-up fraction can be anentirely new treatment session or fraction (e.g., requiring a newpatient setup), or simply a continuation of the incomplete fraction(e.g., without requiring a new patient setup) from the point where theinterruption has occurred. If the make-up fraction requires a newpatient setup, the different setup error might cause a so-called fieldjunctioning error, which may result in underdosing or overdosing part(s)of the tumor target region and/or critical structures. Junctioningerrors may be mitigated using a method similar to that described aboveand depicted in FIG. 6 . The fluence or dose delivered to the patientuntil the interruption occurred may be calculated. This calculateddelivered fluence and/or dose may be compared to the planned fluenceand/or dose. The fluence and/or dose difference between the deliveredand planned fluence and/or dose Δf may be used to update the RFM. Thefluence Δf may then be delivered to the patient using the updated RFM ina later treatment session or fraction.

One variation of a method for continuing radiation therapy after aninterruption where the patient remains on the platform or couch beforeand after the interruption (i.e., a continuation of the interruptiontreatment session, using the same patient setup parameters and pre-scanimage) may comprise continuing the interrupted shuttle pass by movingthe patient platform to the beam station where the interruptionoccurred, and resuming radiation delivery using the same normalizationfactor as was used before the interruption, and calculating thenormalization factor for the next shuttle pass based on imaging dataacquired during before the interruption and the imaging data acquiredafter the interruption. The normalization factor for the shuttle passfollowing the interruption may be calculated by taking the differencebetween D_(plan) and the sum of the radiation delivered during thecompleted shuttle passes, the partial shuttle pass before theinterruption, and the resumed partial shuttle pass after theinterruption, and normalizing the difference over the predictedcumulated fluence that would be delivered if each of the future shuttlepasses delivered the same amount of radiation as was delivered in theinterrupted pass (i.e., the radiation delivered during the partialshuttle pass before the interruption and the resumed partial shuttlepass after the interruption). For example, the normalization factork_(i) for a treatment session with N total shuttle passes and theinterrupt occurred in the m^(th) pass may be calculated as follows:

D_(i−1,calc) is defined as the delivered dose for the i−1 pass asdefined previously. The numerator is calculated as the difference of theD_(plan) and sum of D_(i−1,calc) for all previous passes.

$k_{i} = \left\{ \begin{matrix}{\frac{D_{plan} - D_{{i - 1},{calc}}}{D_{{i - 1},{{predicted}{cumulative}}}},{{{for}1} \leq i \leq m}} \\{\frac{D_{plan} - \left( {D_{{i - 1},{calc}} + D_{m,{{pre} - {interrupt}}} + D_{m,{{post} - {interrupt}}}} \right)}{D_{{i - 1},{{predicted}{cumulative}}}},{{{for}i} = {m + 1}}} \\{\frac{D_{plan} - \left( {D_{p - 1} + D_{{i - 1},{calc}}} \right)}{D_{{i - 1},{{predicted}{cumulative}}}},{{{for}i} > {m + 1}}}\end{matrix} \right.$

Where D_(p−1)=(D_(i−1,calc)+D_(m,pre-interrupt)) and D_(plan),D_(i,calc), etc. are calculated as described previously.

FIG. 15A depicts one variation of a method of radiation delivery whenthere has been an interruption during a shuttle pass and the patientremains on the platform to continue the interrupted treatment session(i.e., no new pre-scan image). Method (1500) may comprise calculating(1502) the cumulative radiation dose applied to the patient untiltreatment was interrupted in the m^(th) pass(D_(delivered_before_interrupt)) of N total shuttle passes, storing(1504) the cumulative radiation dose D_(delivered_before_interrupt), thenormalization factor k_(m) for the m^(th) pass, and the patient platformlocation when treatment was interrupted in system memory, and resumingradiation delivery (1506) for the m^(th) pass by moving the patientplatform to the location (e.g., beam station) where treatment wasinterrupted, and emitting radiation fluence, where the emitted fluenceis scaled by k_(m). The radiation delivered in the resumed m^(th)partial pass may be calculated as follows:D _(partial mth pass) =k _(m)β_(m)[(x _(m,post-interrupt)*RFM)∘BFZ]

The method (1500) may comprise calculating (1508) a predicted cumulativefluence based on the imaging data acquired during the m^(th) pass, bysumming over N passes, calculating (1510) a normalization factor k_(m+1)for the next pass, based on the predicted cumulative fluence, applying(1512) an (m+1)^(th) pass of radiation while acquiring imaging data,where the emitted radiation fluence is calculated based on the acquiredimaging data and the calculated normalization factor k_(m+1), andcalculating (1514) normalization factor k_(m+2) and apply an (m+2)^(th)pass of radiation based on imaging data acquired during the (m+2)^(th)pass until N passes have been completed. The predicted cumulativefluence may be calculated (1508) as follows:D _(m,predicted cumulative)=Σ_(j=m) ^(N)β_(j) D _(m,raw), whereD _(m,raw)=((x _(m,pre-interrupt)*RFM)∘BFZ)+((x_(m,post-interrupt)*RFM)∘BFZ)

The normalization factor k_(m+1) may be calculated (1510) as follows:

$k_{m + 1} = \frac{D_{plan} - \left( {D_{{delivered},{{pre} - {interrupt}}} + D_{{partial}{mth}{pass}}} \right)}{D_{m,{{predicted}{cumulative}}}}$

For example, if radiation delivery is interrupted in the second shuttlepass (without for a new setup or new pre-scan image), the second shuttlepass may be resumed using the normalization factor k₂ (i.e., same as wasbefore the interruption), and the normalization factor for subsequentshuttle passes may be calculated as follows:

${k_{i} = \frac{D_{plan} - \left( {{k_{1}\beta_{1}D_{1.{raw}}} + {\sum_{j = 2}^{i - 1}{k_{j}\beta_{j}D_{j,{raw}}}}} \right)}{\left( {\sum_{j = i}^{N}\beta_{j}} \right)D_{j,{raw}}}},{{{for}i} = {3:N}}$

FIG. 16 is a plot that depicts the cumulative fluence as a function ofbeam station for a treatment session with four shuttle passes, where thetreatment was interrupted at the second shuttle pass, with variousinterruption characteristics to evaluate and characterize the accuracyof the above-described method for handling treatment interruptions ascompared with a treatment session without any interruptions (line withcross shaped bullets). The value of dampening factor used for thissimulation is (α=1/1.2). The line with the square-shaped bulletsrepresents the planned fluence and the line with the cross-shapedbullets represents the fluence delivered after four shuttle passeswithout any interruptions. The line with the diamond-shaped bulletsrepresents the fluence delivered after four shuttle passes with a singleinterruption in the middle of the second shuttle pass. The line with thestar-shaped bullets represents the fluence delivered after four shuttlepasses with a single interruption at the end of the second shuttle passas the couch is changing directions between the second pass and thethird pass. The line with the circle-shaped bullets represents thefluence delivered after four shuttle passes with a three interruptions.As depicted in the plot, updating the normalization factor with thefluence emitted before and after the interruption helps the average ofthe cumulative delivered radiation fluence to converge toward theaverage planned radiation fluence despite the interruptions in thetreatment session. The fluence curves for the treatment sessions withinterruptions (i.e., lines with diamond-, star-, and circle-shapedbullets) track closely with the curve for the treatment session withoutinterruptions (i.e., line with cross-shaped bullets).

In some variations, radiation delivery is unable (or not desired) to beresumed in the same session and the patient may be removed from thesystem and scheduled to resume treatment on an another occasion. Forexample, the patient may feel too ill to proceed with radiation deliveryon a particular day and/or radiation therapy system components may notfunction within specified tolerances and cannot be calibrated with thepatient in the bunker. When the patient returns to resume radiationdelivery, a new set up and new pre-scan image may be acquired. In somevariations, the patient platform may be moved to the location and/orbeam station where the interruption occurred in the previous treatment.Radiation delivery methods may account for the new setup and/or pre-scanimage and the radiation fluence that was delivered in the previous,interrupted session when calculating a normalization factor for resumingradiation delivery. FIG. 15B depicts one variation of a radiationdelivery method where the radiation delivered may be adjusted by anormalization factor that is derived at least in part based on theradiation fluence delivered in a prior treatment session and a pre-scanimage acquired for the current session is depicted in FIG. 15B. Method(1520) may comprise calculating (1522) the cumulative radiation doseapplied to the patient until treatment was interrupted in the m^(th)pass (D_(delivered_before_interrupt)) of N total passes, storing (1524)the cumulative radiation dose D_(delivered_before_interrupt), thenormalization factor k_(m) for the m^(th) pass, and the patient platformlocation when treatment was interrupted in system memory (e.g., locationalong the IEC-Y axis and/or beam station index), and after the patienthas returned to the radiation therapy system, acquiring (1526) a newpre-scan image of patient (e.g., a PET and/or CT image X_(p_prescan))and calculating a normalization factor k_(p)__(m) based on theX_(p_prescan), and resuming (1528) radiation delivery in the m^(th) passby moving the patient platform to the location where treatment wasinterrupted, and emitting radiation fluence, where the emitted fluenceis scaled by k_(p_m). The normalization factor k_(p_m) may be calculated(1526) as follows:

$k_{p\_ m} = \frac{D_{plan}}{\left( {D_{p_{prescan}} \times \frac{{treatment}{time}}{{prescan}{time}}} \right)}$

Where D_(plan), β_(j) are as described previously, and D_(p) _(prescan)is the radiation fluence calculated based on the new pre-scan imageX_(p_prescan). The radiation fluence delivered (1528) to resume theinterrupted m^(th) shuttle pass may be determined (1528) as follows:D _(partial mth pass) =k _(p_m)β_(m)[(x _(m,post-interrupt)*RFM)∘BFZ]

Where x_(m,post-interrupt) is the imaging data acquired in the m^(th)shuttle pass after the interruption. Method (1520) may also comprisecalculating (1530) a predicted cumulative fluence based on the imagingdata acquired during the m^(th) pass, by summing over N passes,calculating (1532) a normalization factor k_(m+1) for the next pass,based on the predicted cumulative fluence, applying (1534) an (m+1)^(th)pass of radiation while acquiring imaging data, where the emittedradiation fluence is calculated based on the acquired imaging data andthe calculated normalization factor k_(m+1), and optionally calculating(1536) a normalization factor k_(m+2) and applying an (m+2)^(th) pass ofradiation based on imaging data acquired during the (m+2)^(th) passuntil N passes have been completed. The predicted cumulative fluence maybe calculated (1530) as follows:D _(m,predicted cumulative)=Σ_(j=m) ^(N)β_(j) D _(m,raw), whereD _(m,raw)=((x _(m,pre-interrupt)*RFM)∘BFZ)+((x_(m,post-interrupt)*RFM)∘BFZ)

Where x_(m, pre-interrupt) comprises the imaging data acquired in them^(th) shuttle pass before the interrupt, and x_(m, post-interrupt)comprises the imaging data acquired in the m^(th) shuttle pass after theinterrupt (i.e., resuming the interrupted shuttle pass). Thenormalization factor k_(m+1) may be calculated (1532) as follows:

$k_{m + 1} = \frac{D_{plan} - \left( {D_{{{delivered}\_{before}}{\_{interrupt}}} + D_{{{partial}{mth}{pass}})}} \right.}{D_{m,{{predicted}{cumulative}}}}$

Where D_(delivered_before_interrupt) is the cumulative radiation fluencedelivered before the interrupted shuttle pass and D_(partial mth pass)is the radiation fluence delivered during the resumed interrupted pass(e.g., the portion of the m^(th) pass that was undelivered due to theinterruption).

Controller

A system (e.g., a treatment planning system, radiation therapy system)that may be configured to deliver therapeutic radiation to a patient maycomprise a controller in communication with the imaging system of theradiation therapy system and/or the therapeutic radiation source and/orthe multi-leaf collimator and/or gantry. The controller may comprise oneor more processors and one or more machine-readable memories incommunication with the one or more processors, which may be configuredto execute or perform any of the methods described herein (e.g., themethods described and depicted in FIGS. 4, 5, 6, 7, 8A-8C, 10, 15A-15B).The controller of a radiation therapy system may be connected to orother systems by wired or wireless communication channels. In somevariations, the controller of a treatment planning system may be locatedin the same or different room as the patient. For example, thecontroller may be coupled to a patient platform or disposed on a trolleyor medical cart adjacent to the patient and/or operator.

The controller may be implemented consistent with numerous generalpurpose or special purpose computing systems or configurations. Variousexemplary computing systems, environments, and/or configurations thatmay be suitable for use with the systems and devices disclosed hereinmay include, but are not limited to software or other components withinor embodied on personal computing devices, network appliances, serversor server computing devices such as routing/connectivity components,portable (e.g., hand-held) or laptop devices, multiprocessor systems,microprocessor-based systems, and distributed computing networks.

Examples of portable computing devices include smartphones, cell phones,tablet PCs, phablets (personal computing devices that are larger than asmartphone, but smaller than a tablet), and the like.

Processor

In some embodiments, a processor may be any suitable processing deviceconfigured to run and/or execute a set of instructions or code and mayinclude one or more data processors, image processors, graphicsprocessing units, physics processing units, digital signal processors,and/or central processing units. The processor may be, for example, ageneral purpose processor, Field Programmable Gate Array (FPGA), anApplication Specific Integrated Circuit (ASIC), or the like. Theprocessor may be configured to run and/or execute application processesand/or other modules, processes and/or functions associated with thesystem and/or a network associated therewith. The underlying devicetechnologies may be provided in a variety of component types, e.g.,metal-oxide semiconductor field-effect transistor (MOSFET) technologieslike complementary metal-oxide semiconductor (CMOS), bipolartechnologies like emitter-coupled logic (ECL), polymer technologies(e.g., silicon-conjugated polymer and metal-conjugated polymer-metalstructures), mixed analog and digital, or the like.

Memory

In some embodiments, memory may include a database and may be, forexample, a random access memory (RAM), a memory buffer, a hard drive, anerasable programmable read-only memory (EPROM), an electrically erasableread-only memory (EEPROM), a read-only memory (ROM), Flash memory, etc.The memory may store instructions to cause the processor to executemodules, processes and/or functions associated with the system, such asone or more treatment plans, full or high SNR images, partial or low SNRimages, the calculation of fluence maps based on treatment plan and/orclinical goals, segmentation of fluence maps into radiation therapysystem instructions (e.g., that may direct the operation of the gantry,therapeutic radiation source, multi-leaf collimator, and/or any othercomponents of a radiation therapy system and/or diagnostic or treatmentplanning system), normalization factors, dampening factors, calculatedand/or measured quantities of delivered or emitted radiation fluence ordose, patient platform or couch positions, and image and/or dataprocessing associated with treatment planning and/or delivery.

Some embodiments described herein relate to a computer storage productwith a non-transitory computer-readable medium (also may be referred toas a non-transitory processor-readable medium) having instructions orcomputer code thereon for performing various computer-implementedoperations. The computer-readable medium (or processor-readable medium)is non-transitory in the sense that it does not include transitorypropagating signals per se (e.g., a propagating electromagnetic wavecarrying information on a transmission medium such as space or a cable).The media and computer code (also may be referred to as code oralgorithm) may be those designed and constructed for the specificpurpose or purposes. Examples of non-transitory computer-readable mediainclude, but are not limited to, magnetic storage media such as harddisks, floppy disks, and magnetic tape; optical storage media such asCompact Disc/Digital Video Discs (CD/DVDs); Compact Disc-Read OnlyMemories (CD-ROMs), and holographic devices; magneto-optical storagemedia such as optical disks; solid state storage devices such as a solidstate drive (SSD) and a solid state hybrid drive (SSHD); carrier wavesignal processing modules; and hardware devices that are speciallyconfigured to store and execute program code, such asApplication-Specific Integrated Circuits (ASICs), Programmable LogicDevices (PLDs), Read-Only Memory (ROM), and Random-Access Memory (RAM)devices. Other embodiments described herein relate to a computer programproduct, which may include, for example, the instructions and/orcomputer code disclosed herein.

A user interface may serve as a communication interface between anoperator or clinician and the radiation therapy system. The userinterface may comprise an input device and output device (e.g., touchscreen and display) and be configured to receive input data and outputdata from one or more of the support arm, external magnet, sensor,delivery device, input device, output device, network, database, andserver. Sensor data from one or more sensors may be received by userinterface and output visually, audibly, and/or through haptic feedbackby one or more output devices. As another example, operator control ofan input device (e.g., joystick, keyboard, touch screen) may be receivedby user and then processed by processor and memory for user interface tooutput a control signal to the radiation therapy system components(e.g., gantry, MLC, therapeutic radiation source, imaging systems, PETdetectors, etc.).

Some variations of a radiation therapy system for delivering therapeuticradiation may comprise a display device that may allow an operator toview graphical and/or textual representations of fluence maps, and/ordose distributions, and/or regions of interest, and/or volumes ofinterest, and/or patient anatomical images, and/or patient data (e.g.,physiological and/or biological), DVH curves, dose plots, and the like.In some variations, an output device may comprise a display deviceincluding at least one of a light emitting diode (LED), liquid crystaldisplay (LCD), electroluminescent display (ELD), plasma display panel(PDP), thin film transistor (TFT), organic light emitting diodes (OLED),electronic paper/e-ink display, laser display, and/or holographicdisplay.

Communication

In some embodiments, a treatment planning system and/or radiationtherapy system may be in communication with other computing devices via,for example, one or more networks, each of which may be any type ofnetwork (e.g., wired network, wireless network). A wireless network mayrefer to any type of digital network that is not connected by cables ofany kind. Examples of wireless communication in a wireless networkinclude, but are not limited to cellular, radio, satellite, andmicrowave communication. However, a wireless network may connect to awired network in order to interface with the Internet, other carriervoice and data networks, business networks, and personal networks. Awired network is typically carried over copper twisted pair, coaxialcable and/or fiber optic cables. There are many different types of wirednetworks including wide area networks (WAN), metropolitan area networks(MAN), local area networks (LAN), Internet area networks (IAN), campusarea networks (CAN), global area networks (GAN), like the Internet, andvirtual private networks (VPN). Hereinafter, network refers to anycombination of wireless, wired, public and private data networks thatare typically interconnected through the Internet, to provide a unifiednetworking and information access system.

Cellular communication may encompass technologies such as GSM, PCS, CDMAor GPRS, W-CDMA, EDGE or CDMA2000, LTE, WiMAX, and 5G networkingstandards. Some wireless network deployments combine networks frommultiple cellular networks or use a mix of cellular, Wi-Fi, andsatellite communication. In some embodiments, the systems, apparatuses,and methods described herein may include a radiofrequency receiver,transmitter, and/or optical (e.g., infrared) receiver and transmitter tocommunicate with one or more devices and/or networks.

While various inventive variations have been described and illustratedherein, those of ordinary skill in the art will readily envision avariety of other means and/or structures for performing the functionand/or obtaining the results and/or one or more of the advantagesdescribed herein, and each of such variations and/or modifications isdeemed to be within the scope of the inventive embodiments describedherein. More generally, those skilled in the art will readily appreciatethat all parameters, dimensions, materials, and configurations describedherein are meant to be exemplary and that the actual parameters,dimensions, materials, and/or configurations will depend upon thespecific application or applications for which the inventive teachingsis/are used. Those skilled in the art will recognize, or be able toascertain using no more than routine experimentation, many equivalentsto the specific inventive variations described herein. It is, therefore,to be understood that the foregoing variations are presented by way ofexample only and that, within the scope of the appended claims andequivalents thereto, inventive variations may be practiced otherwisethan as specifically described and claimed. Inventive variations of thepresent disclosure are directed to each individual feature, system,article, material, kit, and/or method described herein. In addition, anycombination of two or more such features, systems, articles, materials,kits, and/or methods, if such features, systems, articles, materials,kits, and/or methods are not mutually inconsistent, is included withinthe inventive scope of the present disclosure.

The invention claimed is:
 1. A method for radiation delivery, the method comprising: delivering at least two separate quantities of radiation to a patient moving on a patient platform, wherein the radiation is delivered to the patient in at least two separate passes of the patient platform within the radiation therapy system in a single treatment session.
 2. The method of claim 1, wherein the at least two separate quantities of radiation comprise a first quantity of radiation and a second quantity of radiation, and wherein the second quantity of radiation is different from the first quantity of radiation.
 3. The method of claim 1, wherein moving the patient comprises moving the platform to a series of pre-defined platform locations.
 4. The method of claim 1, further comprising delivering a third separate quantity of radiation in a third pass of the patient platform within the radiation therapy system in the single treatment session.
 5. The method of claim 1, wherein the at least two separate passes comprise a first pass and a second pass, wherein moving the patient in the first pass comprises moving the platform from a first location to a second location such that the patient passes through a radiation treatment beam plane of a therapeutic radiation source.
 6. The method of claim 5, wherein moving the patient in the second pass comprises moving the platform from the second location to the first location such that the patient passes through the radiation treatment beam plane.
 7. The method of claim 6, further comprising moving the patient through the radiation treatment beam plane in a third pass and to deliver a third quantity of radiation in the third pass, and wherein moving the patient in the third pass comprises moving the platform from the first location to the second location.
 8. The method of claim 1, wherein the at least two separate quantities of radiation comprise a first quantity of radiation and a second quantity of radiation, and wherein delivering the first quantity of radiation comprises emitting radiation with a therapeutic radiation source according to one or more radiation delivery parameters, and wherein the method further comprises updating the one or more radiation delivery parameters and delivering the second quantity of radiation according to the updated one or more radiation delivery parameters.
 9. The method of claim 8, further comprising calculating a cumulative quantity of radiation that has been delivered after each pass, calculating a radiation fluence difference by comparing the cumulative delivered quantity of radiation with a planned quantity of radiation, and updating the one or more radiation delivery parameters based on the calculated radiation fluence difference.
 10. The method of claim 9, wherein calculating the cumulative quantity of radiation that has been delivered comprises using MV detector data located across from the therapeutic radiation source.
 11. The method of claim 9, wherein the one or more radiation delivery parameters comprises radiation therapy system machine instructions.
 12. The method of claim 11, wherein the radiation therapy system machine instructions comprise jaw, multi-leaf collimator, platform, and/or gantry instructions.
 13. The method of claim 9, wherein the one or more radiation delivery parameters comprises a radiation fluence to be delivered in a pass, and wherein delivering the second quantity of radiation comprises updating the radiation fluence according to the radiation fluence to be delivered in a pass.
 14. The method of claim 9, further comprising delivering the calculated radiation fluence difference in a subsequent pass.
 15. The method of claim 1, further comprising calculating a cumulative quantity of radiation that has been delivered after each pass.
 16. The method of claim 1, wherein the quantity of radiation delivered in a pass of the patient platform is derived from imaging data acquired during a previous pass of the patient platform.
 17. The method of claim 16, wherein the imaging data are selected from a group consisting of: positron annihilation emission data, kV X-ray data, MRI sub-samplings in k space, and MV detector data.
 18. The method of claim 1, wherein the at least two separate quantities of radiation comprise a first quantity of radiation and a second quantity of radiation, and wherein the method further comprises acquiring imaging data while delivering the first quantity of radiation and deriving the second quantity of radiation from the acquired imaging data.
 19. The method of claim 18, wherein the imaging data are selected from a group consisting of: positron annihilation emission data, kV X-ray data, MRI sub-samplings in k space, and MV detector data. 